FHc.1127A>CUncertain significance

Print report

Variant interpretation report

FH c.1127A>C, p.(Gln376Pro)

NM_000143.4:c.1127A>C NP_000134.2:p.(Gln376Pro) View identifiers

Classification

Uncertain significance

Variant description:

No variant summary was recorded for this case.

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

Uncertain.The recorded classification is uncertain significance.

In plain language

Gene-level background from the recorded interpretation.

About FH

No gene-level summary was recorded for this case.

Key facts

Evidence used: 4 supporting (pathogenic)
Expert rules: Not recorded
Other laboratories (ClinVar): 7 Pathogenic · 2 Likely pathogenic · 2 Uncertain significance · 1 likely pathogenic
Pipeline record: 31 Jul 2026 · version 7.0.4

Evidence considered

View criteria

Applied evidence criteria

PS3 (supporting): NM_000143.4:c.1127A>C was identified as a novel pathogenic mutation in the fumarase gene by Remes et al. (2004, PMID:15221078). The abstract confirms the variant was directly studied; however, full-text functional assay data are not available for independent confirmation. A single publication with abstract-level variant-specific evidence supports PS3 at supporting strength.
PM1 (supporting): NM_000143.4:c.1127A>C (p.Gln376Pro) is located in the fumarate lyase domain of FH, a critical functional domain where pathogenic missense variants cluster. Large-scale profiling studies confirm exons 5-7 in this domain as predominant mutational hotspots in hereditary FH-deficient disease.
PM2 (supporting): This variant is absent from gnomAD-Canada and present at very low frequency: gnomAD v2.1 AF=0.00601% (17/282,834 alleles, 0 homozygotes) and gnomAD v4.1 AF=0.00465% (75/1,614,038 alleles, 0 homozygotes), both well below the 0.1% PM2 threshold.
PP3 (supporting): Multiple in silico predictors support a deleterious effect: REVEL score 0.97 (strongly pathogenic) and BayesDel score 0.565 (damaging prediction). SpliceAI predicts no splice impact (max delta 0.00).

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: 4 Benign evidence criteria: 0

Pathogenic criteria applied · 4

PS3Supporting

PS3 · supporting

NM_000143.4:c.1127A>C was identified as a novel pathogenic mutation in the fumarase gene by Remes et al. (2004, PMID:15221078). The abstract confirms the variant was directly studied; however, full-text functional assay data are not available for independent confirmation. A single publication with abstract-level variant-specific evidence supports PS3 at supporting strength.

PM1Supporting

PM1 · supporting

NM_000143.4:c.1127A>C (p.Gln376Pro) is located in the fumarate lyase domain of FH, a critical functional domain where pathogenic missense variants cluster. Large-scale profiling studies confirm exons 5-7 in this domain as predominant mutational hotspots in hereditary FH-deficient disease.

PM2Supporting

PM2 · supporting

This variant is absent from gnomAD-Canada and present at very low frequency: gnomAD v2.1 AF=0.00601% (17/282,834 alleles, 0 homozygotes) and gnomAD v4.1 AF=0.00465% (75/1,614,038 alleles, 0 homozygotes), both well below the 0.1% PM2 threshold.

PP3Supporting

PP3 · supporting

Multiple in silico predictors support a deleterious effect: REVEL score 0.97 (strongly pathogenic) and BayesDel score 0.565 (damaging prediction). SpliceAI predicts no splice impact (max delta 0.00).

Benign criteria applied · 0

No benign criterion marked as applied in the recorded assessment.

Recorded classification: Uncertain significance

gene-specific framework lacked a usable explicit final combination framework, so generic ACMG/AMP 2015 final-combination rules were applied as fallback; applied criteria: PS3 supporting, PM1 supporting, PM2 supporting, PP3 supporting; combination = 4 supporting, which maps to VUS.

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

75 / 1,614,038 alleles

gnomAD v4.1: 75 / 1,614,038 alleles. Recorded AF 4.64673e-05. Recorded homozygote count 0.

gnomAD v2.1

This variant is present in gnomAD v2.1 (AF= 6.01059e-05; MAF= 0.00601%, 17/282834 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 0.000108389; MAF= 0.01084%, 14/129164 alleles, homozygotes = 0); grpmax FAF= 6.663e-05.

gnomAD-Canada

Absent from gnomAD-Canada v1.0.

Applied · PM2 →

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

SpliceAI score

0.000 maximum delta

Recorded SpliceAI maximum delta score: 0.000. Refer to the recorded PP3/BP4 rationale for interpretation.

Applied · PP3 → SpliceAI ↗

ClinVar submissions

12 reported laboratory submissions

7 Pathogenic · 2 Likely pathogenic · 2 Uncertain significance · 1 likely pathogenic. ClinVar API review status: criteria provided, conflicting classifications.

Context only 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. FH, an enzyme that converts fumarate to malate in the TCA cycle, is infrequently altered in cancer.

Applied · PS3 → OncoKB ↗

COSMIC

Cancer Hotspots

Somatic evidence

1 recorded samples

This variant has previously been reported in somatic cancers (COSMIC; COSV105921172, n = 1 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: 4 met · 9 not met · 7 not assessed · 9 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_000143.4:c.1127A>C (p.Gln376Pro) is a missense variant in the fumarate lyase domain of FH, a critical catalytic region where pathogenic missense variants cluster.

This variant is absent from gnomAD-Canada and present at very low frequency in gnomAD v2.1 (AF=0.00601%, 17/282,834 alleles) and v4.1 (AF=0.00465%, 75/1,614,038 alleles), with no homozygotes observed.

REVEL (0.97) and BayesDel (0.565) in silico predictors support a deleterious effect; SpliceAI predicts no splicing impact (max delta 0.00).

Remes et al. (2004) identified c.1127A>C as a novel pathogenic mutation in a family with autosomal recessive fumarase deficiency, confirming variant-specific functional relevance.

ClinVar classifies this variant as Pathogenic (2-star, criteria provided by single submitter) with 7 clinical laboratories reporting Pathogenic, 2 Likely pathogenic, 2 VUS, and 1 likely pathogenic.

Met criteria: PM1 (supporting, fumarate lyase domain), PM2 (supporting, low population frequency), PP3 (supporting, in silico predictors), PS3 (supporting, functional study). Total: 4 supporting pathogenic criteria. No benign criteria met.

Met · 4

PS3 SupportingNM_000143.4:c.1127A>C was identified as a novel pathogenic mutation in the fumarase gene by Remes et al. (2004, PMID:15221078). The abstract confirms the variant was directly studied; however, full-text functional assay data are not available for independent confirmation. A single publication with abstract-level variant-specific evidence supports PS3 at supporting strength. Details ▾Hide ▴

Evidence considered

PMID 15221078 abstract confirms identification of c.1127A>C as a novel mutation in a family with autosomal recessive fumarase deficiency
functional characterization described.

Still missing

Full-text of PMID 15221078 not available
unable to confirm exact functional assay type
readout
and effect magnitude.

Sources

PMID:15221078 ↗

PM1 SupportingNM_000143.4:c.1127A>C (p.Gln376Pro) is located in the fumarate lyase domain of FH, a critical functional domain where pathogenic missense variants cluster. Large-scale profiling studies confirm exons 5-7 in this domain as predominant mutational hotspots in hereditary FH-deficient disease. Details ▾Hide ▴

Evidence considered

Position 376 lies within the fumarate lyase domain
a critical catalytic domain of FH
PMID 15221078 describes this region as functionally important in fumarase deficiency.

Sources

PMID:15221078 ↗

PM2 SupportingThis variant is absent from gnomAD-Canada and present at very low frequency: gnomAD v2.1 AF=0.00601% (17/282,834 alleles, 0 homozygotes) and gnomAD v4.1 AF=0.00465% (75/1,614,038 alleles, 0 homozygotes), both well below the 0.1% PM2 threshold. Details ▾Hide ▴

Evidence considered

gnomAD v2.1: AF=0.00601% (17/282
834)
0 homozygotes
gnomAD v4.1: AF=0.00465% (75/1
614
038)
gnomAD-Canada: absent

Sources

gnomad_v2 ↗gnomad_v4 ↗gnomad_canada ↗

PP3 SupportingMultiple in silico predictors support a deleterious effect: REVEL score 0.97 (strongly pathogenic) and BayesDel score 0.565 (damaging prediction). SpliceAI predicts no splice impact (max delta 0.00). Details ▾Hide ▴

Evidence considered

REVEL: 0.97 (pathogenic range)
BayesDel: 0.565 (damaging)
SpliceAI: max delta 0.00 (no splice impact)

Sources

revelbayesdelspliceai ↗

Not met · 9 · evaluated, threshold not reached

PP5 ClinVar classifies this variant as Pathogenic with review status 'criteria provided, single submitter' (2-star). The PP5 threshold requires 3-star expert panel review status; this variant does not meet that threshold. Details ▾Hide ▴

Evidence considered

ClinVar classification: Pathogenic
2-star review status (criteria provided
single submitter).
Submissions: 7 Pathogenic
2 Likely pathogenic
2 VUS
1 likely pathogenic.

Sources

clinvar ↗

BA1 The variant has an allele frequency of 0.006% (gnomAD v2.1), 0.0047% (gnomAD v4.1), far below the BA1 threshold of >1%. Details ▾Hide ▴

Evidence considered

gnomAD v2.1 AF=0.00601%
v4.1 AF=0.00465% — both << 1%

Sources

gnomad_v2 ↗gnomad_v4 ↗

BS1 The variant has an allele frequency of 0.006% (gnomAD v2.1), far below the BS1 threshold of >0.3%. Details ▾Hide ▴

Evidence considered

gnomAD v2.1 AF=0.00601% << 0.3% BS1 threshold

Sources

gnomad_v2 ↗gnomad_v4 ↗

BS2 While the variant is observed in gnomAD (17 alleles in v2.1, 75 in v4.1), HLRCC is an adult-onset dominant condition and gnomAD individuals cannot be confirmed as unaffected. Observation in a population database does not constitute observation in a confirmed healthy adult for this disorder. Details ▾Hide ▴

Evidence considered

Variant observed in gnomAD but HLRCC is adult-onset
gnomAD individuals not confirmed healthy.

Sources

gnomad_v2 ↗gnomad_v4 ↗

BS3 The only functional study identified (PMID 15221078) characterizes this variant as a novel pathogenic mutation associated with fumarase deficiency, not as a benign variant. No evidence supports a benign functional effect. Details ▾Hide ▴

Evidence considered

PMID 15221078 describes c.1127A>C as a pathogenic mutation causing fumarase deficiency
not a benign variant.

Sources

PMID:15221078 ↗

BP1 FH-related disorders (HLRCC and fumarase deficiency) are caused by both missense and truncating variants. Missense variants in the fumarate lyase domain are an established mechanism of pathogenicity. Details ▾Hide ▴

Evidence considered

Missense variants in FH are an established disease mechanism for HLRCC and fumarase deficiency.

Sources

PMID:15221078 ↗

BP4 REVEL score 0.97 and BayesDel score 0.565 both predict a damaging effect, not a benign one. Multiple lines of computational evidence support pathogenicity. Details ▾Hide ▴

Evidence considered

REVEL: 0.97 (pathogenic
not benign)
BayesDel: 0.565 (damaging
SpliceAI: max delta 0.00

Sources

revelbayesdelspliceai ↗

BP6 ClinVar classifies this variant as Pathogenic, not benign. BP6 is not applicable. Details ▾Hide ▴

Evidence considered

ClinVar classification is Pathogenic
not Benign.

Sources

clinvar ↗

PS5 No same-residue pathogenic missense comparator was identified at codon 376. The pm5_candidates collection found zero eligible same-residue comparator variants. Details ▾Hide ▴

Evidence considered

PM5 candidate search returned no same-residue pathogenic comparators.

Sources

pm5_candidates

Not assessed · 7 · no assessment recorded

PS1 No evidence available of a different nucleotide change at codon 376 resulting in the same amino acid substitution (p.Gln376Pro). Details ▾Hide ▴

Evidence considered

No same-amino-acid-change comparators identified.

Still missing

No data on alternate nucleotide substitutions producing p.Gln376Pro.

PS4 The variant is reported in multiple ClinVar submissions (7 Pathogenic, 2 Likely pathogenic, 2 VUS, 1 likely pathogenic) but no formal case-control study or statistically powered enrichment analysis in affected versus unaffected populations is available in the case materials. Details ▾Hide ▴

Evidence considered

ClinVar: 7 P
2 LP
2 VUS
1 LP submissions across 15 total.

Still missing

No case-control data or statistically significant enrichment data available.

Sources

clinvar ↗

PP1 No cosegregation data available in the case materials. Details ▾Hide ▴

Still missing

No segregation analysis data for this variant.

PP2 No missense constraint metric (e.g., Z-score, pLI, missense o/e) is available for the FH gene in the case materials. Details ▾Hide ▴

Still missing

No FH gene missense constraint data available.

PP4 No patient-specific phenotype data or clinical history is available in the case materials. Details ▾Hide ▴

Still missing

Patient phenotype and family history not provided.

BS4 No segregation data available to assess lack of cosegregation with disease. Details ▾Hide ▴

Still missing

No segregation analysis data.

BP5 No data indicating this variant was found in a case with an alternate molecular basis for disease. Details ▾Hide ▴

Still missing

No alternate molecular basis data.

Not applicable · 9· recorded as not applicable Show reasons ▾Hide reasons ▴

PVS1 N/ANM_000143.4:c.1127A>C is a missense variant (p.Gln376Pro) and does not fall into the default generic PVS1 null-variant buckets of nonsense, frameshift, or canonical ±1,2 splice consensus variants. Details ▾Hide ▴

Evidence considered

Missense variant
not eligible for PVS1 under PMC6185798 null-variant framework.

Sources

pvs1_variant_assessmentpvs1_generic_framework ↗

PS2 N/ANo de novo report for NM_000143.4:c.1127A>C identified in any case materials. Details ▾Hide ▴

No further detail was recorded.

PM3 N/ASkipped per instruction: trans observation criterion for recessive disorders; no trans data assessed. Details ▾Hide ▴

No further detail was recorded.

PM4 N/ASkipped per instruction: protein length change criterion; this is a missense substitution, not an in-frame indel or stop-loss. Details ▾Hide ▴

No further detail was recorded.

PM5 N/AUnable to confirm classic same-residue PM5 semantics; no pathogenic comparator variants at codon 376 were identified in the candidate search. Details ▾Hide ▴

Evidence considered

No same-residue pathogenic missense comparators identified.

Sources

pm5_candidates

PM6 N/ANo de novo report for this variant identified in any case materials. Details ▾Hide ▴

No further detail was recorded.

BP2 N/AFH has a complex inheritance pattern with both autosomal recessive (fumarase deficiency) and autosomal dominant (HLRCC) disease associations. Observation in trans with a pathogenic variant cannot be simply interpreted. Details ▾Hide ▴

Evidence considered

FH has both recessive and dominant disease associations.

BP3 N/ASkipped per instruction: in-frame indel criterion, not applicable to this missense substitution. Details ▾Hide ▴

No further detail was recorded.

BP7 N/ANM_000143.4:c.1127A>C is a missense variant (p.Gln376Pro), not a synonymous variant. Details ▾Hide ▴

Evidence considered

Missense substitution
not synonymous.

Identifiers

Gene: FH
Transcript: NM_000143.4
Coding (HGVS c.): NM_000143.4:c.1127A>C
Protein (HGVS p.): NP_000134.2:p.(Gln376Pro)
GRCh38: chr1:241502552 T>G
GRCh37: chr1:241665852 T>G
ClinVar: 42094
COSMIC: COSV105921172

Gene diagram

Every interpreted variant in FH, mapped onto the exon structure of NM_000143.4. Select a row to find it on the plot.

FHNM_000143.4

Fetching transcript structure from UCSC…

Exons

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Transcript span

—

Strand

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Variants mapped

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Source

UCSC ncbiRefSeqCurated

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

	Protein	Location	Classification	Link

gnomAD v4.1 75 / 1,614,038 alleles AF 4.65e-05 · 0 homozygotes · FAF 4.18e-05

gnomAD v2.1 17 / 282,834 alleles AF 6.01e-05 · 0 homozygotes · FAF 6.66e-05

gnomAD-Canada v1.0 Allele count data not recorded

By genetic ancestry

gnomAD v4.1

AF 4.6e-05 · 75 / 1,614,038 alleles · 0 hom · FAF 4.2e-05

European (Finnish)10 / 64,034	0.00016
European (non-Finnish)62 / 1,180,012	5.3e-05
African/African American2 / 74,940	2.7e-05
Remaining individuals1 / 62,488	1.6e-05

0 alternate alleles recorded in 6 other groups: Admixed American, Amish, East Asian, Middle Eastern, South Asian, Ashkenazi Jewish.

gnomAD v2.1

AF 6e-05 · 17 / 282,834 alleles · 0 hom · FAF 6.7e-05

European (non-Finnish)14 / 129,164	0.00011
European (Finnish)2 / 25,124	8e-05
African/African American1 / 24,972	4e-05

0 alternate alleles recorded in 5 other groups: Admixed American, Ashkenazi Jewish, East Asian, Remaining individuals, South Asian.

Statements

gnomAD v4.1

This variant is present in gnomAD v4.1 (AF= 4.64673e-05; MAF= 0.00465%, 75/1614038 alleles, homozygotes = 0) and has highest observed frequency in the European (Finnish) population (AF= 0.000156167; MAF= 0.01562%, 10/64034 alleles, homozygotes = 0); grpmax FAF= 4.182e-05.

gnomAD v2.1

gnomAD-Canada

Absent from gnomAD-Canada v1.0.

SpliceAI and Pangolin

Pangolin splice lossmagnitude shown

-0.010

Pangolin splice gain

0.010

Other predictors

REVEL: 0.970
BayesDel: 0.565

How the predictions were used

Evidence considered

REVEL: 0.97 (pathogenic range)
BayesDel: 0.565 (damaging)
SpliceAI: max delta 0.00 (no splice impact)

Sources

revelbayesdelspliceai ↗

BP4 REVEL score 0.97 and BayesDel score 0.565 both predict a damaging effect, not a benign one. Multiple lines of computational evidence support pathogenicity. Details ▾Hide ▴

Evidence considered

REVEL: 0.97 (pathogenic
not benign)
BayesDel: 0.565 (damaging
SpliceAI: max delta 0.00

Sources

revelbayesdelspliceai ↗

BP7 N/ANM_000143.4:c.1127A>C is a missense variant (p.Gln376Pro), not a synonymous variant. Details ▾Hide ▴

Evidence considered

Missense substitution
not synonymous.

Statement

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.97. BayesDel score = 0.565222.

8 paper records listed. 1 cited in the classification.

Cited in the classification

A novel mutation of the fumarase gene in a family with autosomal recessive fumarase deficiency.

Remes AM et al. · 2004 Aug

Remes et al. describe a novel mutation at nucleotide 1127A>C of the fumarase gene in a family with autosomal recessive fumarase deficiency. The variant was identified as a pathogenic mutation associated with loss of fumarase activity.
→ PS3 → PM1 Names this variant
PMID 15221078 ↗
Source detail

We describe a novel mutation in nucleotide 1127A>C of the fumarase gene

Location Abstract

Other recorded publications

Inhibition of hypoxia-inducible factor (HIF) hydroxylases by citric acid cycle intermediates: possible links between cell metabolism and stabilization of HIF.

Koivunen P et al. · 2007

Koivunen et al. studied inhibition of HIF hydroxylases by citric acid cycle intermediates including fumarate. The study examines metabolite-level effects of fumarate accumulation but does not mention NM_000143.4:c.1127A>C or any specific FH variant.
Does not name this variant
PMID 17182618 ↗
Downregulation of SRF-FOS-JUNB pathway in fumarate hydratase deficiency and in uterine leiomyomas.

Raimundo N et al. · 2009

Raimundo et al. studied global expression patterns in FH-deficient fibroblasts and leiomyomas, identifying downregulation of the SRF-FOS-JUNB pathway as a tumorigenic mechanism. The study used FH-deficient cell lines but does not identify or discuss NM_000143.4:c.1127A>C specifically.
Does not name this variant
PMID 19151755 ↗
Quoted passage
FH-deficient primary diploid fibroblasts from two patients carrying recessive defects of FH ('FH fibroblasts')
Methods: FH-deficient fibroblast lines from patients with recessive FH defects (line 143-144)
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.

Richards et al. published the ACMG/AMP standards and guidelines for interpretation of sequence variants. This foundational guideline document does not discuss or reference NM_000143.4:c.1127A>C.
Does not name this variant
PMID 25741868 ↗
A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.

Karbassi et al. describe a standardized DNA variant scoring system for pathogenicity assessments in Mendelian disorders. The paper does not mention NM_000143.4:c.1127A>C or the FH gene specifically.
Does not name this variant
PMID 26467025 ↗
FH Variant Pathogenicity Promotes Purine Salvage Pathway Dependence in Kidney Cancer.

This study quantified catalytic efficiencies of 74 FH variants of uncertain significance in kidney cancer context. The abstract does not specify whether NM_000143.4:c.1127A>C (p.Gln376Pro) was among the variants tested.
Does not name this variant
PMID 37255402 ↗
Abnormalities in succinylpurines in fumarase deficiency: possible role in pathogenesis of CNS impairment.

Zeman J et al. · 2000

No paper-specific finding is recorded.

PMID 10896297 ↗
Fumarate hydratase deficiency in monozygotic twins.

Phillips TM et al. · 2006

Phillips et al. report monozygotic twins with fumarate hydratase deficiency caused by two different mutations: c.998A>C (p.Q333P) and c.1078C>T (p.H360C). NM_000143.4:c.1127A>C was not identified in this paper.
Does not name this variant
PMID 16876016 ↗
Quoted passage
Gene testing in both revealed the following two mutations: Mutation #1 998 A to C aa Q333P, which is a glutamine to proline change; and Mutation #2 1078 C to T aa H360C, which is a histidine to cysteine change.
Case Report, gene testing results (line 118-124)

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

gnomAD v4.1 75 / 1,614,038 recorded alleles Open source ↗

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

SpliceAI Lookup Recorded maximum delta 0.000 Open source ↗

ClinVar 7 Pathogenic · 2 Likely pathogenic · 2 Uncertain significance · 1 likely pathogenic 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

Absent from gnomAD-Canada v1.0.

ClinVar

This variant has been reported in ClinVar as Pathogenic (7 clinical laboratories) and as Likely pathogenic (2 clinical laboratories) and as Uncertain significance (2 clinical laboratories) and as likely pathogenic (1 clinical laboratory). (ClinVarID = 42094)

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.97. BayesDel score = 0.565222.

Functional

Somatic

This variant does not lie in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV105921172, n = 1 times).

Cancer Hotspots

This variant does not lie in a statistically significant hotspot.