SDHAc.163T>CBenign

Print report

Variant interpretation report

SDHA c.163T>C, p.(Tyr55His)

NM_004168.4:c.163T>C NP_004159.2:p.(Tyr55His) View identifiers

Classification

Benign

Variant description:

No variant summary was recorded for this case.

Five-step scale from benign to pathogenic. This variant is benign. Select a step to read what it means.

Benign.A benign classification under the recorded framework.

In plain language

Gene-level background from the recorded interpretation.

About SDHA

No gene-level summary was recorded for this case.

Key facts

Evidence used: 1 stand alone (benign) · 1 strong (benign) · 3 supporting (benign)
Expert rules: Not recorded
Other laboratories (ClinVar): 6 Benign · 4 Likely benign · 1 benign
Pipeline record: 29 May 2026

Evidence considered

View criteria

Applied evidence criteria

BA1 (stand alone): This variant has an allele frequency exceeding 1% in the East Asian population across multiple population databases: gnomAD v2.1 East Asian AF = 1.96% (391/19,954 alleles, 5 homozygotes), gnomAD v4.1 East Asian AF = 2.39% (1,074/44,890 alleles, 10 homozygotes), and gnomAD-Canada v1.0 East Asian AF = 1.12% (15/1,338 alleles). The gnomAD v4.1 grpmax FAF is 2.27%, well above the 1% BA1 threshold. This allele frequency is too high to support a causative role in rare Mendelian disease, meeting BA1 (stand-alone benign).
BS1 (strong): The allele frequency in the East Asian population exceeds 0.3% in all queried population databases: gnomAD v2.1 EAS AF = 1.96%, gnomAD v4.1 EAS AF = 2.39%, gnomAD-Canada EAS AF = 1.12%. The overall frequency is also elevated in gnomAD v2.1 (0.148%) although below 0.3% in gnomAD v4.1 (0.077%). BS1 is met based on the East Asian subpopulation frequency, which is well above the 0.3% threshold. Note: BA1 (stand-alone benign) is also met; BS1 provides additional population-frequency support but is not counted independently when BA1 is applied.
BS2 (supporting): This variant has been observed in the homozygous state in multiple individuals across gnomAD databases: 6 homozygotes in v2.1 (exomes), 12 homozygotes in v4.1 (of which 10 are East Asian), and 0 homozygotes in gnomAD-Canada. SDHA biallelic loss-of-function causes severe, early-onset recessive conditions (mitochondrial complex II deficiency, Leigh syndrome) with expected full penetrance. The observation of 12 apparently healthy adult homozygotes in population databases is inconsistent with a highly penetrant recessive pathogenic variant. BS2 is met at the supporting benign level.
BP4 (supporting): Multiple in silico predictors consistently suggest a benign effect for this missense variant. REVEL score is 0.392 (below the commonly used 0.5 pathogenic threshold). BayesDel score is 0.00237 (very low, strongly favoring benign). SpliceAI predicts no significant splice alteration (max delta score = 0.03). The convergent computational evidence supports a lack of functional impact, meeting BP4 at the supporting benign level.
BP6 (supporting): This variant has been reported in ClinVar as Benign by 6 clinical laboratories, Likely benign by 4 clinical laboratories, and benign by 1 clinical laboratory (ClinVar Variation ID: 353201). The aggregate ClinVar consensus is Benign/Likely benign with 11 submitting laboratories, though none represent an expert panel. BP6 is met at the supporting benign level based on the consistent benign classification across multiple clinical testing laboratories.

LYFE Sciences is an AI system, and it can make mistakes. Criteria may be applied incorrectly, sources may be misread, and a confident-looking classification can still be wrong. Double-check every criterion and its underlying evidence before relying on any call.

01The reasoning

How it was classified

The recorded framework is Not recorded. The criteria and strengths shown below come from the saved assessment; this page does not recalculate the classification.

Recorded applied criteria

The applied criteria and their strengths are shown as assessed under the stated framework.

Pathogenic evidence criteria: 0 Benign evidence criteria: 5

Pathogenic criteria applied · 0

No pathogenic criterion marked as applied in the recorded assessment.

Benign criteria applied · 5

BA1Stand alone

BA1 · stand alone

This variant has an allele frequency exceeding 1% in the East Asian population across multiple population databases: gnomAD v2.1 East Asian AF = 1.96% (391/19,954 alleles, 5 homozygotes), gnomAD v4.1 East Asian AF = 2.39% (1,074/44,890 alleles, 10 homozygotes), and gnomAD-Canada v1.0 East Asian AF = 1.12% (15/1,338 alleles). The gnomAD v4.1 grpmax FAF is 2.27%, well above the 1% BA1 threshold. This allele frequency is too high to support a causative role in rare Mendelian disease, meeting BA1 (stand-alone benign).

BS1Strong

BS1 · strong

The allele frequency in the East Asian population exceeds 0.3% in all queried population databases: gnomAD v2.1 EAS AF = 1.96%, gnomAD v4.1 EAS AF = 2.39%, gnomAD-Canada EAS AF = 1.12%. The overall frequency is also elevated in gnomAD v2.1 (0.148%) although below 0.3% in gnomAD v4.1 (0.077%). BS1 is met based on the East Asian subpopulation frequency, which is well above the 0.3% threshold. Note: BA1 (stand-alone benign) is also met; BS1 provides additional population-frequency support but is not counted independently when BA1 is applied.

BS2Supporting

BS2 · supporting

This variant has been observed in the homozygous state in multiple individuals across gnomAD databases: 6 homozygotes in v2.1 (exomes), 12 homozygotes in v4.1 (of which 10 are East Asian), and 0 homozygotes in gnomAD-Canada. SDHA biallelic loss-of-function causes severe, early-onset recessive conditions (mitochondrial complex II deficiency, Leigh syndrome) with expected full penetrance. The observation of 12 apparently healthy adult homozygotes in population databases is inconsistent with a highly penetrant recessive pathogenic variant. BS2 is met at the supporting benign level.

BP4Supporting

BP4 · supporting

Multiple in silico predictors consistently suggest a benign effect for this missense variant. REVEL score is 0.392 (below the commonly used 0.5 pathogenic threshold). BayesDel score is 0.00237 (very low, strongly favoring benign). SpliceAI predicts no significant splice alteration (max delta score = 0.03). The convergent computational evidence supports a lack of functional impact, meeting BP4 at the supporting benign level.

BP6Supporting

BP6 · supporting

This variant has been reported in ClinVar as Benign by 6 clinical laboratories, Likely benign by 4 clinical laboratories, and benign by 1 clinical laboratory (ClinVar Variation ID: 353201). The aggregate ClinVar consensus is Benign/Likely benign with 11 submitting laboratories, though none represent an expert panel. BP6 is met at the supporting benign level based on the consistent benign classification across multiple clinical testing laboratories.

Recorded classification: Benign

gene-specific framework lacked a usable explicit final combination framework, so generic ACMG/AMP 2015 final-combination rules were applied as fallback; applied criteria: BA1 stand-alone benign, BS1 strong benign, BS2 supporting benign, BP4 supporting benign, BP6 supporting benign; combination = 1 stand-alone benign, which maps to Benign.

02The sources

Evidence at a glance

Evidence summaries and captured source records, where available. Missing entries should not be interpreted as negative findings.

gnomAD v4.1

gnomAD v2.1

Population frequency

1,241 / 1,613,346 alleles

gnomAD v4.1: 1,241 / 1,613,346 alleles. Recorded AF 0.000769209. Recorded homozygote count 12.

gnomAD v2.1

This variant is present in gnomAD v2.1 (AF= 0.00147924; MAF= 0.14792%, 418/282578 alleles, homozygotes = 6) and has highest observed frequency in the East Asian population (AF= 0.0195951; MAF= 1.95951%, 391/19954 alleles, homozygotes = 5); grpmax FAF= 0.0180621.

gnomAD-Canada

This variant is present in gnomAD-Canada v1.0 (AF= 0.00124891; MAF= 0.12489%, 23/18416 alleles, homozygotes = 0) and has highest observed frequency in the eas population (AF= 0.0112108; grpmax FAF95= 0.00690997).

Applied · BA1, BS1, BS2 →

gnomAD v4.1 ↗gnomAD v2.1 ↗gnomAD-Canada ↗

SpliceAI score

0.030 maximum delta

Recorded SpliceAI maximum delta score: 0.030. Refer to the recorded PP3/BP4 rationale for interpretation.

Applied · BP4 → SpliceAI ↗

ClinVar submissions

11 reported laboratory submissions

6 Benign · 4 Likely benign · 1 benign.

Applied · BP6 → ClinVar ↗

Functional evidence

Statement recorded

OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. SDHA, a subunit of succinate dehydrogenase, is frequently altered by amplification in various cancers, including lung and bladder cancers.

No listed criterion applied OncoKB ↗

COSMIC

Cancer Hotspots

Somatic evidence

5 recorded samples

This variant has previously been reported in somatic cancers (COSMIC; COSV53768747, n = 5 times).

Cancer Hotspots

This variant does not lie in a statistically significant hotspot.

Context only

COSMIC ↗Cancer Hotspots ↗

For specialists

Technical detail

ACMG/AMP criteria under Not recorded, with the data and sources behind each one.

29 criteria with recorded statuses: 5 met · 6 not met · 13 not assessed · 5 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.

Pathogenic

PVS1 PS1 PS2 PS3 PS4 PM1 PM2 PM3 PM4 PM5 PM6 PP1 PP2 PP3 PP4 PP5 PS5

Benign

BA1 BS1 BS2 BS3 BS4 BP1 BP2 BP3 BP4 BP5 BP6 BP7

Met Not met Not assessed Not applicable

NM_004168.4:c.163T>C (p.Tyr55His) is classified as Benign based on the ACMG/AMP 2015 framework.

This variant meets BA1 (stand-alone benign): the allele frequency in the East Asian population is 1.96% in gnomAD v2.1 (391/19,954 alleles, 5 homozygotes) and 2.39% in gnomAD v4.1 (1,074/44,890 alleles, 10 homozygotes), with a gnomAD v4.1 grpmax FAF of 2.27%. An allele frequency exceeding 1% in a general population is inconsistent with a role in rare Mendelian disease.

Additional benign evidence includes BS1 (East Asian AF well above 0.3%), BS2 (12 homozygotes observed in gnomAD v4.1 in a gene where biallelic loss-of-function causes severe early-onset recessive disease), BP4 (REVEL = 0.392; BayesDel = 0.00237; SpliceAI max delta = 0.03; all predictors converge on a benign interpretation), and BP6 (ClinVar consensus of Benign/Likely benign from 11 clinical laboratories).

No pathogenic criteria are met. PVS1 is not applicable (missense variant). PP3 is not met (in silico predictors favor benign). PM1 is not met (the variant is common in population databases despite lying in the FAD-binding domain). PS4 is not met (the variant is classified as benign across clinical laboratories and observed at appreciable frequency in unaffected populations).

The classification of Benign is driven by BA1, which alone is sufficient to classify a variant as Benign under the ACMG/AMP 2015 combination rules.

Met · 5

BA1 Stand aloneThis variant has an allele frequency exceeding 1% in the East Asian population across multiple population databases: gnomAD v2.1 East Asian AF = 1.96% (391/19,954 alleles, 5 homozygotes), gnomAD v4.1 East Asian AF = 2.39% (1,074/44,890 alleles, 10 homozygotes), and gnomAD-Canada v1.0 East Asian AF = 1.12% (15/1,338 alleles). The gnomAD v4.1 grpmax FAF is 2.27%, well above the 1% BA1 threshold. This allele frequency is too high to support a causative role in rare Mendelian disease, meeting BA1 (stand-alone benign). Details ▾Hide ▴

Evidence considered

gnomAD v2.1 EAS AF = 1.96%
5 homozygotes
gnomAD v4.1 EAS AF = 2.39%
10 homozygotes
gnomAD-Canada EAS AF = 1.12%
v4.1 grpmax FAF = 2.27%

Sources

gnomad_v2 ↗gnomad_v4 ↗gnomad_canada ↗

BS1 StrongThe allele frequency in the East Asian population exceeds 0.3% in all queried population databases: gnomAD v2.1 EAS AF = 1.96%, gnomAD v4.1 EAS AF = 2.39%, gnomAD-Canada EAS AF = 1.12%. The overall frequency is also elevated in gnomAD v2.1 (0.148%) although below 0.3% in gnomAD v4.1 (0.077%). BS1 is met based on the East Asian subpopulation frequency, which is well above the 0.3% threshold. Note: BA1 (stand-alone benign) is also met; BS1 provides additional population-frequency support but is not counted independently when BA1 is applied. Details ▾Hide ▴

Evidence considered

gnomAD v2.1 EAS AF = 1.96% (>0.3%)
gnomAD v4.1 EAS AF = 2.39% (>0.3%)
gnomAD-Canada EAS AF = 1.12% (>0.3%)

Sources

gnomad_v2 ↗gnomad_v4 ↗gnomad_canada ↗

BS2 SupportingThis variant has been observed in the homozygous state in multiple individuals across gnomAD databases: 6 homozygotes in v2.1 (exomes), 12 homozygotes in v4.1 (of which 10 are East Asian), and 0 homozygotes in gnomAD-Canada. SDHA biallelic loss-of-function causes severe, early-onset recessive conditions (mitochondrial complex II deficiency, Leigh syndrome) with expected full penetrance. The observation of 12 apparently healthy adult homozygotes in population databases is inconsistent with a highly penetrant recessive pathogenic variant. BS2 is met at the supporting benign level. Details ▾Hide ▴

Evidence considered

v2.1: 6 homozygotes
v4.1: 12 homozygotes (10 in East Asian)
Recessive SDHA disorders have full early penetrance

Sources

gnomad_v2 ↗gnomad_v4 ↗

BP4 SupportingMultiple in silico predictors consistently suggest a benign effect for this missense variant. REVEL score is 0.392 (below the commonly used 0.5 pathogenic threshold). BayesDel score is 0.00237 (very low, strongly favoring benign). SpliceAI predicts no significant splice alteration (max delta score = 0.03). The convergent computational evidence supports a lack of functional impact, meeting BP4 at the supporting benign level. Details ▾Hide ▴

Evidence considered

REVEL = 0.392 (<0.5
benign)
BayesDel = 0.00237 (benign)
SpliceAI max delta = 0.03 (no splice impact)

Sources

revelbayesdelspliceai ↗

BP6 SupportingThis variant has been reported in ClinVar as Benign by 6 clinical laboratories, Likely benign by 4 clinical laboratories, and benign by 1 clinical laboratory (ClinVar Variation ID: 353201). The aggregate ClinVar consensus is Benign/Likely benign with 11 submitting laboratories, though none represent an expert panel. BP6 is met at the supporting benign level based on the consistent benign classification across multiple clinical testing laboratories. Details ▾Hide ▴

Evidence considered

ClinVar: Benign (6 labs)
Likely benign (4 labs)
benign (1 lab)
Total 11 submissions with benign/LB consensus

Sources

clinvar ↗

Not met · 6 · evaluated, threshold not reached

PS4 No case-control study demonstrating a statistically significant enrichment of this variant in affected individuals compared to controls was identified. ClinVar submissions report the variant as Benign/Likely benign across multiple clinical laboratories, which is inconsistent with PS4. The observed population frequency in gnomAD (v4.1 total AF = 0.077%, v2.1 total AF = 0.148%) further argues against disease association. Details ▾Hide ▴

Evidence considered

gnomAD population frequencies inconsistent with pathogenic prevalence
ClinVar consensus is Benign/Likely benign

Still missing

No formal case-control study

Sources

gnomad_v2 ↗gnomad_v4 ↗clinvar ↗

PM1 Residue Tyr55 lies within the FAD-binding domain of SDHA (Rossmann-fold motif). However, no ClinGen- or VCEP-defined mutational hotspot or critical domain specification exists for SDHA PM1 adjudication. Furthermore, gnomAD population data show the variant is common in East Asian populations (AF ~2%), and multiple homozygotes are observed (n=10-12), which is inconsistent with a critical functional domain where missense variation is absent or rare. PM1 is not met. Details ▾Hide ▴

Evidence considered

Tyr55 is in the FAD-binding domain
gnomAD East Asian AF ~2% with homozygotes argues against a PM1 domain

Still missing

No gene-specific PM1 domain specification from ClinGen

Sources

gnomad_v2 ↗gnomad_v4 ↗

PM2 In gnomAD v4.1, the total allele frequency is 0.00077 (0.077%), which is below the 0.1% threshold. However, in gnomAD v2.1, the total AF is 0.00148 (0.148%), above 0.1%. More critically, BA1 is met (East Asian AF >1% in both v2.1 and v4.1), which is mutually exclusive with PM2. PM2 is not applied. Details ▾Hide ▴

Evidence considered

v2.1 total AF = 0.148% (>0.1%)
v4.1 total AF = 0.077% (<0.1%)
BA1 is met
precluding PM2

Sources

gnomad_v2 ↗gnomad_v4 ↗gnomad_canada ↗

PP3 Multiple in silico predictors suggest a benign effect for this missense variant. REVEL score is 0.392 (below the 0.5 threshold typically used for damaging prediction). BayesDel score is 0.00237 (very low, indicating benign). SpliceAI predicts no splice impact (max delta = 0.03). The computational evidence does not support a damaging effect; thus PP3 is not met. Details ▾Hide ▴

Evidence considered

REVEL = 0.392 (non-damaging)
BayesDel = 0.00237 (benign)
SpliceAI max delta = 0.03 (no splice impact)

Sources

revelbayesdelspliceai ↗

PP5 PP5 requires a reputable source to have recently reported the variant as pathogenic. In ClinVar, this variant is classified as Benign by 6 clinical laboratories, Likely benign by 4, and benign by 1. No submitter classifies this variant as pathogenic or likely pathogenic. PP5 is not met. Details ▾Hide ▴

Evidence considered

ClinVar consensus: Benign/Likely benign (11 submissions)
No pathogenic assertion from any submitter

Sources

clinvar ↗

BP1 BP1 applies to missense variants in genes where primarily truncating variants are known to cause disease. While SDHA has pathogenic truncating variants, it also has well-established pathogenic missense variants associated with PPGL, GIST, and Leigh syndrome. The gene does not meet the criterion that primarily truncating variants cause disease; therefore BP1 is not met. Details ▾Hide ▴

Evidence considered

SDHA has both pathogenic missense and truncating variants

Not assessed · 13 · no assessment recorded

PS1 No alternate nucleotide change at the same amino acid position with an established pathogenic classification was identified. PS1 cannot be applied without a known pathogenic comparator with the same amino acid change from a different nucleotide substitution. Details ▾Hide ▴

Still missing

No same-amino-acid pathogenic comparator identified

PS2 No de novo occurrence of this variant in a patient with disease and confirmed paternity/maternity was identified in the literature or databases. No case report or database entry explicitly states a de novo observation of p.Tyr55His. Details ▾Hide ▴

Still missing

No de novo reports found in literature or databases

PS3 No published functional studies specifically evaluating the functional impact of NM_004168.4:c.163T>C (p.Tyr55His) were identified. The Kent et al. 2024 paper (PMID:39321216) describes an SDHA functional assay platform but does not specifically mention this variant in the available abstract, and no full-text is available for confirmation. Well-established functional evidence showing a damaging effect is absent. Details ▾Hide ▴

Still missing

No variant-specific functional studies found
PMID:39321216 may contain relevant data but full-text unavailable for confirmation

Sources

PMID:39321216 ↗

PM3 No reports of this variant occurring in trans with a known pathogenic or likely pathogenic variant in a recessive SDHA-associated disorder (e.g., mitochondrial complex II deficiency, Leigh syndrome) were identified. Details ▾Hide ▴

Still missing

No biallelic observations with pathogenic variants in recessive disease contexts

PM5 Automated PM5 candidate harvesting was unable to identify same-residue comparator variants with pathogenic classifications satisfying classic PM5 semantics. No alternate missense at Tyr55 with a known pathogenic classification was found. PM5 cannot be applied. Details ▾Hide ▴

Still missing

No pathogenic comparator at same residue (Tyr55)

PM6 No assumed de novo observation (without confirmation of paternity/maternity) was identified for this variant. No clinical testing report or publication lists p.Tyr55His as a de novo finding. Details ▾Hide ▴

Still missing

No de novo reports (confirmed or unconfirmed)

PP1 No family cosegregation data were identified for NM_004168.4:c.163T>C. No multi-case family study mentioning this variant with segregation analysis was found. Details ▾Hide ▴

Still missing

No family segregation studies found

PP2 PP2 requires a low rate of benign missense variation and a high rate of pathogenic missense variants in the gene. SDHA has both pathogenic missense and truncating variants reported in association with PPGL, GIST, and Leigh syndrome. However, gene-specific missense constraint metrics (e.g., gnomAD missense Z-score, regional constraint) were not comprehensively assessed, and the observed high population frequency of this specific missense (East Asian AF ~2%) complicates a generic PP2 application. PP2 is not assessed without formal gene-level missense constraint evaluation. Details ▾Hide ▴

Still missing

No formal gene-level missense constraint metrics evaluated

PP4 PP4 requires patient-specific phenotypic and family history information that is highly specific for the disease. No proband-specific clinical data were provided in this case. PP4 is not assessable without detailed patient phenotype information. Details ▾Hide ▴

Still missing

No proband phenotype data available

BS3 No well-established functional studies demonstrating a neutral (non-damaging) effect of NM_004168.4:c.163T>C (p.Tyr55His) were identified. The Kent et al. 2024 paper (PMID:39321216) describes an SDHA functional assay platform but does not specifically mention this variant in the available abstract, and no full-text is available for confirmation. BS3 cannot be assessed without variant-specific functional data. Details ▾Hide ▴

Still missing

No variant-specific functional studies showing neutral effect

Sources

PMID:39321216 ↗

BS4 No evidence of non-segregation of this variant with disease in affected families was identified. No report of an affected family member lacking the variant within a family segregating SDHA-associated disease was found. Details ▾Hide ▴

Still missing

No non-segregation data available

BP2 No observation of this variant in trans with a pathogenic variant for a fully penetrant dominant disorder, or in cis with a pathogenic variant in any inheritance pattern, was identified. No co-occurrence or phasing data were found in gnomAD or published literature for this specific variant. Details ▾Hide ▴

Still missing

No co-occurrence/phase data with known pathogenic variants

BP5 BP5 applies when an alternate molecular basis for disease has been identified in a case with a different pathogenic variant. No such information is available for this case. Details ▾Hide ▴

Still missing

No proband data
alternate molecular basis cannot be evaluated

Not applicable · 5· recorded as not applicable Show reasons ▾Hide reasons ▴

PVS1 N/ANM_004168.4:c.163T>C is a missense variant (p.Tyr55His), not a predicted null variant. It does not fall into the default generic PVS1 buckets of nonsense, frameshift, or canonical ±1,2 splice consensus variants. SpliceAI predicts no significant splice impact (max delta score = 0.03). The generic PVS1 framework is not applicable. Details ▾Hide ▴

Evidence considered

Missense variant
not null
SpliceAI max delta = 0.03 (no splice impact)

Sources

pvs1_generic_framework ↗spliceai ↗

PM4 N/APM4 applies to protein-length-altering variants (in-frame deletions/insertions, stop-loss). NM_004168.4:c.163T>C is a single-nucleotide missense substitution. PM4 is not applicable. Details ▾Hide ▴

Evidence considered

Missense variant
not a protein-length change

BP3 N/ABP3 applies to in-frame deletions or insertions in repetitive regions without known function. NM_004168.4:c.163T>C is a single-nucleotide missense substitution. BP3 is not applicable. Details ▾Hide ▴

Evidence considered

Missense variant
not an in-frame indel in a repetitive region

BP7 N/ABP7 applies to synonymous (silent) variants for which splicing prediction algorithms predict no impact on the splice consensus sequence. NM_004168.4:c.163T>C is a missense variant (p.Tyr55His), not a synonymous variant. BP7 is not applicable. Details ▾Hide ▴

Evidence considered

Missense variant
not synonymous

PS5 N/APS5 applies when a different nucleotide change at the same position has been reported as pathogenic. No such established pathogenic variant at the same nucleotide position was identified. Details ▾Hide ▴

No further detail was recorded.

Identifiers

Gene: SDHA
Transcript: NM_004168.4
Coding (HGVS c.): NM_004168.4:c.163T>C
Protein (HGVS p.): NP_004159.2:p.(Tyr55His)
GRCh38: chr5:224372 T>C
GRCh37: chr5:224487 T>C
ClinVar: 353201, 1357856
COSMIC: COSV53768747

Gene diagram

Every interpreted variant in SDHA, mapped onto the exon structure of NM_004168.4. Select a row to find it on the plot.

SDHANM_004168.4

Fetching transcript structure from UCSC…

Exons

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Transcript span

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Strand

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Variants mapped

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Source

UCSC ncbiRefSeqCurated

All variants in SDHA — Select a row to find it on the plot; use the link to open its page.

	Protein	Location	Classification	Link

gnomAD v4.1 1,241 / 1,613,346 alleles AF 0.000769 · 12 homozygotes · FAF 0.0227

gnomAD v2.1 418 / 282,578 alleles AF 0.00148 · 6 homozygotes · FAF 0.0181

gnomAD-Canada v1.0 23 / 18,416 alleles AF 0.00125 · 0 homozygotes · FAF 0.00691

By genetic ancestry

gnomAD v4.1

AF 0.00077 · 1241 / 1,613,346 alleles · 12 hom · FAF 0.023

East Asian1074 / 44,890	0.02410 hom
Remaining individuals74 / 62,426	0.00121 hom
South Asian68 / 91,040	0.000751 hom
African/African American12 / 75,046	0.00016
Admixed American1 / 60,030	1.7e-05
European (non-Finnish)12 / 1,179,712	1e-05

0 alternate alleles recorded in 4 other groups: European (Finnish), Amish, Middle Eastern, Ashkenazi Jewish.

gnomAD v2.1

AF 0.0015 · 418 / 282,578 alleles · 6 hom · FAF 0.018

East Asian391 / 19,954	0.025 hom
South Asian20 / 30,616	0.000651 hom
Remaining individuals3 / 7,220	0.00042
African/African American1 / 24,962	4e-05
European (non-Finnish)3 / 128,894	2.3e-05

0 alternate alleles recorded in 3 other groups: Admixed American, Ashkenazi Jewish, European (Finnish).

gnomAD-Canada

AF 0.0012 · 23 / 18,416 alleles · 0 hom · FAF 0.0069

eas15 / 1,338	0.011
oth2 / 1,138	0.0018
sas2 / 1,362	0.0015
nfe4 / 11,738	0.00034

0 alternate alleles recorded in 5 other groups: afr, amr, asj, fin, mid.

Statements

gnomAD v4.1

This variant is present in gnomAD v4.1 (AF= 0.000769209; MAF= 0.07692%, 1241/1613346 alleles, homozygotes = 12) and has highest observed frequency in the East Asian population (AF= 0.0239252; MAF= 2.39252%, 1074/44890 alleles, homozygotes = 10); grpmax FAF= 0.0227368.

gnomAD v2.1

gnomAD-Canada

Open the gnomAD-Canada detail page →

SpliceAI and Pangolin

SpliceAI acceptor lossat -189 bp

0.030

SpliceAI acceptor gainat -12 bp

0.000

SpliceAI donor lossat -32 bp

0.010

SpliceAI donor gainat +35 bp

0.020

Pangolin splice lossmagnitude shown

-0.010

Pangolin splice gain

0.020

Other predictors

REVEL: 0.392
BayesDel: 0.002

How the predictions were used

Evidence considered

REVEL = 0.392 (<0.5
benign)
BayesDel = 0.00237 (benign)
SpliceAI max delta = 0.03 (no splice impact)

Sources

revelbayesdelspliceai ↗

Evidence considered

REVEL = 0.392 (non-damaging)
BayesDel = 0.00237 (benign)
SpliceAI max delta = 0.03 (no splice impact)

Sources

revelbayesdelspliceai ↗

Evidence considered

Missense variant
not synonymous

Statement

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.03). REVEL score = 0.392. BayesDel score = 0.00236504.

11 paper records listed. No publication is explicitly linked to an applied criterion in the recorded metadata. None of the listed paper records explicitly indicates that the variant is named.

Recorded publications

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

No paper-specific finding is recorded.

PMID 25741868 ↗
A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.

No paper-specific finding is recorded.

PMID 26467025 ↗
Genetic and clinical landscape of childhood cerebellar hypoplasia and atrophy.

Sakamoto M et al. · 2022

No paper-specific finding is recorded.

PMID 36305856 ↗
A Novel Human SDHA-Knockout Cell Line Model for the Functional Analysis of Clinically Relevant SDHA Variants.

Kent JD et al. · 2024

No paper-specific finding is recorded.

PMID 39321216 ↗
Mitochondrial DNA-Associated Leigh Syndrome Spectrum.

Adam MP et al. · 1993

No paper-specific finding is recorded.

PMID 20301352 ↗
Single Large-Scale Mitochondrial DNA Deletion Syndromes.

Adam MP et al. · 1993

No paper-specific finding is recorded.

PMID 20301382 ↗
Primary Mitochondrial Disorders Overview.

Adam MP et al. · 1993

No paper-specific finding is recorded.

PMID 20301403 ↗
Hereditary Paraganglioma-Pheochromocytoma Syndromes.

Adam MP et al. · 1993

No paper-specific finding is recorded.

PMID 20301715 ↗
Pheochromocytoma and paraganglioma: an endocrine society clinical practice guideline.

Lenders JW et al. · 2014

No paper-specific finding is recorded.

PMID 24893135 ↗
Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

No paper-specific finding is recorded.

PMID 28492532 ↗
The North American Neuroendocrine Tumor Society Consensus Guidelines for Surveillance and Management of Metastatic and/or Unresectable Pheochromocytoma and Paraganglioma.

No paper-specific finding is recorded.

PMID 33939658 ↗

Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.

gnomAD v4.1 1,241 / 1,613,346 recorded alleles Open source ↗

gnomAD v2.1 Captured gnomAD v2.1 source record Open source ↗

SpliceAI Lookup Recorded maximum delta 0.030 Open source ↗

ClinVar 6 Benign · 4 Likely benign · 1 benign Open source ↗

COSMIC Captured COSMIC source record Open source ↗

Cancer hotspots Captured Cancer Hotspots source record Open source ↗

OncoKB Captured OncoKB source record Open source ↗

All source links

Statements for reports

The evidence statements recorded by the interpretation pipeline. They have not been reinterpreted by the page.

gnomAD v4.1

gnomAD v2.1

gnomAD-Canada

ClinVar

This variant has been reported in ClinVar as Benign (6 clinical laboratories) and as Likely benign (4 clinical laboratories) and as benign (1 clinical laboratory). (ClinVarID = 353201)

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.03). REVEL score = 0.392. BayesDel score = 0.00236504.

Functional

Somatic

This variant does not lie in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV53768747, n = 5 times).

Cancer Hotspots

This variant does not lie in a statistically significant hotspot.