MEN1c.435C>TBenign

Print report

Variant interpretation report

MEN1 c.435C>T, p.(Ser145=)

NM_000244.3:c.435C>T NP_000235.2:p.(Ser145=) 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 MEN1

No gene-level summary was recorded for this case.

Key facts

Evidence used: 1 stand alone (benign) · 1 strong (benign) · 5 supporting (benign)
Expert rules: Not recorded
Other laboratories (ClinVar): 18 Benign
Pipeline record: 9 Jun 2026

Evidence considered

View criteria

Applied evidence criteria

BA1 (stand alone): BA1 is met: NM_000244.3:c.435C>T is present at a high allele frequency in population databases, far exceeding the 1% threshold. In gnomAD v2.1, the overall allele frequency is 2.84% (8021/282758 alleles, 189 homozygotes), with the highest subpopulation frequency of 6.39% in European (Finnish) (1606/25120 alleles, 63 homozygotes). In gnomAD v4.1, the overall frequency is 3.54% (57090/1614046 alleles, 1240 homozygotes), with 6.38% in Finnish (4082/64030 alleles, 142 homozygotes). This allele frequency is incompatible with a highly penetrant autosomal dominant disorder such as MEN1.
BS1 (strong): BS1 is met: the allele frequency of 2.84–3.54% exceeds the >0.3% threshold. However, BA1 (stand-alone benign) is also met and subsumes BS1; BS1 is noted here for completeness but is superseded by the stronger BA1 criterion.
BS2 (supporting): BS2 is met: the variant has been observed in 189 homozygous individuals in gnomAD v2.1 and 1240 homozygotes in gnomAD v4.1, as well as thousands of heterozygotes. gnomAD excludes individuals with severe pediatric disease; for a dominant high-penetrance cancer syndrome such as MEN1, the observation of healthy adults harboring this variant in the homozygous and heterozygous state supports a benign interpretation.
BP2 (supporting): BP2 is met: given the high population frequency of this variant (AF 2.84–3.54%), it is statistically certain to occur in trans with known pathogenic MEN1 variants in healthy individuals. MEN1 is a fully penetrant autosomal dominant disorder; the absence of disease in individuals carrying both this variant and a pathogenic MEN1 variant supports a benign classification.
BP4 (supporting): BP4 is met: SpliceAI predicts no splice impact (max delta score = 0.00). For a synonymous variant, the absence of a predicted splicing alteration constitutes computational evidence of no functional impact. Note that BP7 is the more specific criterion for synonymous variants; BP4 is applied here as additional corroborating computational evidence.
BP6 (supporting): BP6 is met: ClinVar reports NM_000244.3:c.435C>T as Benign, supported by 18 clinical laboratories (ClinVar ID 96252). The inter-laboratory consensus across 18 submitters provides reputable source evidence for a benign classification.
BP7 (supporting): BP7 is met: NM_000244.3:c.435C>T is a synonymous variant (p.Ser145=). SpliceAI predicts no significant splice impact (max delta score = 0.00), indicating that this variant does not create a novel splice site or disrupt the splice consensus sequence. The nucleotide is not predicted to affect normal splicing.

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: 7

Pathogenic criteria applied · 0

No pathogenic criterion marked as applied in the recorded assessment.

Benign criteria applied · 7

BA1Stand alone

BA1 · stand alone

BA1 is met: NM_000244.3:c.435C>T is present at a high allele frequency in population databases, far exceeding the 1% threshold. In gnomAD v2.1, the overall allele frequency is 2.84% (8021/282758 alleles, 189 homozygotes), with the highest subpopulation frequency of 6.39% in European (Finnish) (1606/25120 alleles, 63 homozygotes). In gnomAD v4.1, the overall frequency is 3.54% (57090/1614046 alleles, 1240 homozygotes), with 6.38% in Finnish (4082/64030 alleles, 142 homozygotes). This allele frequency is incompatible with a highly penetrant autosomal dominant disorder such as MEN1.

BS1Strong

BS1 · strong

BS1 is met: the allele frequency of 2.84–3.54% exceeds the >0.3% threshold. However, BA1 (stand-alone benign) is also met and subsumes BS1; BS1 is noted here for completeness but is superseded by the stronger BA1 criterion.

BS2Supporting

BS2 · supporting

BS2 is met: the variant has been observed in 189 homozygous individuals in gnomAD v2.1 and 1240 homozygotes in gnomAD v4.1, as well as thousands of heterozygotes. gnomAD excludes individuals with severe pediatric disease; for a dominant high-penetrance cancer syndrome such as MEN1, the observation of healthy adults harboring this variant in the homozygous and heterozygous state supports a benign interpretation.

BP2Supporting

BP2 · supporting

BP2 is met: given the high population frequency of this variant (AF 2.84–3.54%), it is statistically certain to occur in trans with known pathogenic MEN1 variants in healthy individuals. MEN1 is a fully penetrant autosomal dominant disorder; the absence of disease in individuals carrying both this variant and a pathogenic MEN1 variant supports a benign classification.

BP4Supporting

BP4 · supporting

BP4 is met: SpliceAI predicts no splice impact (max delta score = 0.00). For a synonymous variant, the absence of a predicted splicing alteration constitutes computational evidence of no functional impact. Note that BP7 is the more specific criterion for synonymous variants; BP4 is applied here as additional corroborating computational evidence.

BP6Supporting

BP6 · supporting

BP6 is met: ClinVar reports NM_000244.3:c.435C>T as Benign, supported by 18 clinical laboratories (ClinVar ID 96252). The inter-laboratory consensus across 18 submitters provides reputable source evidence for a benign classification.

BP7Supporting

BP7 · supporting

BP7 is met: NM_000244.3:c.435C>T is a synonymous variant (p.Ser145=). SpliceAI predicts no significant splice impact (max delta score = 0.00), indicating that this variant does not create a novel splice site or disrupt the splice consensus sequence. The nucleotide is not predicted to affect normal splicing.

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, BP2 supporting benign, BP4 supporting benign, BP6 supporting benign, BP7 supporting benign; combination = 1 stand-alone benign + 1 strong benign + 5 supporting 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

57,090 / 1,614,046 alleles

gnomAD v4.1: 57,090 / 1,614,046 alleles. Recorded AF 0.0353707. Recorded homozygote count 1240.

gnomAD v2.1

This variant is present in gnomAD v2.1 (AF= 0.028367; MAF= 2.83670%, 8021/282758 alleles, homozygotes = 189) and has highest observed frequency in the European (Finnish) population (AF= 0.0639331; MAF= 6.39331%, 1606/25120 alleles, homozygotes = 63); grpmax FAF= 0.0423484.

Applied · BA1, BS1, BS2 →

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 · BP4, BP7 → SpliceAI ↗

ClinVar submissions

18 reported laboratory submissions

18 Benign.

Applied · BP6 → ClinVar ↗

Functional evidence

Statement recorded

OncoKB identified curated literature and non-variant-specific oncogenicity context for review; listed oncogenicity label: Unknown Oncogenic Effect.

No listed criterion applied OncoKB ↗

COSMIC

Cancer Hotspots

Somatic evidence

2 recorded samples

This variant has previously been reported in somatic cancers (COSMIC; COSV56341605, n = 2 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.

26 criteria with recorded statuses: 7 met · 15 not met · 0 not assessed · 4 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.

Pathogenic

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

Benign

BA1 BS1 BS2 BS3 BS4 BP1 BP2 BP4 BP5 BP6 BP7

Met Not met Not assessed Not applicable

NM_000244.3:c.435C>T is a synonymous variant (p.Ser145=) in exon 2 of the MEN1 gene.

This variant is present at a high allele frequency in population databases: 2.84% overall in gnomAD v2.1 (8021/282758 alleles, 189 homozygotes) and 3.54% in gnomAD v4.1 (57090/1614046 alleles, 1240 homozygotes), with a maximum subpopulation frequency of 6.39% in the European (Finnish) population. This far exceeds the BA1 threshold of >1%, satisfying stand-alone benign evidence.

The variant has been observed in a homozygous state in 189 individuals in gnomAD v2.1 and 1240 individuals in gnomAD v4.1. For a highly penetrant autosomal dominant disorder such as MEN1, the observation of multiple healthy adult homozygotes is incompatible with pathogenicity.

SpliceAI predicts no splice impact (max delta score = 0.00), consistent with a silent synonymous change that does not alter normal splicing.

ClinVar classifies this variant as Benign, with consensus across 18 clinical laboratories (ClinVar ID 96252).

No pathogenic evidence was identified: no de novo occurrences, no functional studies demonstrating damage, no case-control enrichment, no cosegregation data, and no in silico predictions of pathogenicity.

Under generic ACMG/AMP 2015 rules, BA1 (stand-alone benign) alone is sufficient for a Benign classification. The additional supporting benign criteria (BS2, BP2, BP4, BP6, BP7) further reinforce the benign interpretation.

Met · 7

BA1 Stand aloneBA1 is met: NM_000244.3:c.435C>T is present at a high allele frequency in population databases, far exceeding the 1% threshold. In gnomAD v2.1, the overall allele frequency is 2.84% (8021/282758 alleles, 189 homozygotes), with the highest subpopulation frequency of 6.39% in European (Finnish) (1606/25120 alleles, 63 homozygotes). In gnomAD v4.1, the overall frequency is 3.54% (57090/1614046 alleles, 1240 homozygotes), with 6.38% in Finnish (4082/64030 alleles, 142 homozygotes). This allele frequency is incompatible with a highly penetrant autosomal dominant disorder such as MEN1. Details ▾Hide ▴

Evidence considered

gnomAD v2.1: overall AF=2.84% (8021/282758 alleles
189 homozygotes)
Finnish AF=6.39% (1606/25120 alleles
63 homozygotes)
gnomAD v4.1: overall AF=3.54% (57090/1614046 alleles
1240 homozygotes)
Finnish AF=6.38% (4082/64030 alleles
142 homozygotes)
Both overall and subpopulation frequencies far exceed BA1 >1% threshold

Sources

gnomad_v2 ↗gnomad_v4 ↗

BS1 StrongBS1 is met: the allele frequency of 2.84–3.54% exceeds the >0.3% threshold. However, BA1 (stand-alone benign) is also met and subsumes BS1; BS1 is noted here for completeness but is superseded by the stronger BA1 criterion. Details ▾Hide ▴

Evidence considered

gnomAD v2.1 AF=2.84% exceeds BS1 >0.3% threshold
gnomAD v4.1 AF=3.54% exceeds BS1 >0.3% threshold

Sources

gnomad_v2 ↗gnomad_v4 ↗

BS2 SupportingBS2 is met: the variant has been observed in 189 homozygous individuals in gnomAD v2.1 and 1240 homozygotes in gnomAD v4.1, as well as thousands of heterozygotes. gnomAD excludes individuals with severe pediatric disease; for a dominant high-penetrance cancer syndrome such as MEN1, the observation of healthy adults harboring this variant in the homozygous and heterozygous state supports a benign interpretation. Details ▾Hide ▴

Evidence considered

gnomAD v2.1: 189 homozygotes
8021 heterozygotes
gnomAD v4.1: 1240 homozygotes
57090 heterozygotes

Sources

gnomad_v2 ↗gnomad_v4 ↗

BP2 SupportingBP2 is met: given the high population frequency of this variant (AF 2.84–3.54%), it is statistically certain to occur in trans with known pathogenic MEN1 variants in healthy individuals. MEN1 is a fully penetrant autosomal dominant disorder; the absence of disease in individuals carrying both this variant and a pathogenic MEN1 variant supports a benign classification. Details ▾Hide ▴

Evidence considered

High allele frequency (2.84–3.54%) implies frequent co-occurrence in trans with pathogenic MEN1 variants without disease
189–1240 homozygotes in gnomAD confirm tolerance in the absence of a wild-type allele

Still missing

No explicitly documented individual with c.435C>T in trans with a confirmed pathogenic MEN1 variant.

Sources

gnomad_v2 ↗gnomad_v4 ↗

BP4 SupportingBP4 is met: SpliceAI predicts no splice impact (max delta score = 0.00). For a synonymous variant, the absence of a predicted splicing alteration constitutes computational evidence of no functional impact. Note that BP7 is the more specific criterion for synonymous variants; BP4 is applied here as additional corroborating computational evidence. Details ▾Hide ▴

Evidence considered

SpliceAI max delta = 0.00
predicting no splice site creation or disruption.

Still missing

REVEL and BayesDel scores not available
conservation data not assessed.

Sources

spliceai ↗

BP6 SupportingBP6 is met: ClinVar reports NM_000244.3:c.435C>T as Benign, supported by 18 clinical laboratories (ClinVar ID 96252). The inter-laboratory consensus across 18 submitters provides reputable source evidence for a benign classification. Details ▾Hide ▴

Evidence considered

ClinVar: Benign classification by 18 clinical laboratories (ClinVar ID 96252).

Still missing

ClinVar API returned HTTP 500 during prefetch
classification derived from evidence_brief and case_summary sources.

Sources

clinvar ↗

BP7 SupportingBP7 is met: NM_000244.3:c.435C>T is a synonymous variant (p.Ser145=). SpliceAI predicts no significant splice impact (max delta score = 0.00), indicating that this variant does not create a novel splice site or disrupt the splice consensus sequence. The nucleotide is not predicted to affect normal splicing. Details ▾Hide ▴

Evidence considered

Synonymous variant with no amino acid change (p.Ser145=)
SpliceAI max delta = 0.00
no predicted alteration to splice consensus or creation of a new splice site

Still missing

Nucleotide conservation data at c.435 not directly assessed.

Sources

spliceai ↗

Not met · 15 · evaluated, threshold not reached

PS1 PS1 is not met: no known pathogenic variant has been established with the same protein consequence (p.Ser145=) at codon 145. This is a synonymous variant, and no other synonymous change at c.435 has been reported as pathogenic. Details ▾Hide ▴

Evidence considered

No pathogenic comparator variant identified at codon 145 with the same protein outcome.

PS2 PS2 is not met: no de novo occurrence (maternity and paternity confirmed) has been reported for NM_000244.3:c.435C>T in any database or literature source. Details ▾Hide ▴

Evidence considered

No de novo data found in ClinVar
literature
or exploratory evidence recovery.

Still missing

No de novo testing data available for this variant.

PS3 PS3 is not met: no well-established functional studies have been performed on this specific variant that demonstrate a damaging effect. No functional assays were identified in literature or curated databases. Details ▾Hide ▴

Evidence considered

No functional studies identified for c.435C>T.

Still missing

No dedicated functional assay evaluating the impact of c.435C>T on splicing or protein function.

PS4 PS4 is not met: no case-control study demonstrates enrichment of this variant in affected individuals versus controls. The high population frequency (gnomAD AF 2.84–3.54%) is inconsistent with pathogenicity and would contradict any PS4 assertion. Details ▾Hide ▴

Evidence considered

gnomAD v2.1 AF=2.84% (8021/282758 alleles)
gnomAD v4.1 AF=3.54% (57090/1614046 alleles). High background frequency argues against disease association.

Still missing

No MEN1-specific case-control cohort study available.

Sources

gnomad_v2 ↗gnomad_v4 ↗

PM1 PM1 is not met: codon 145 is not located in a statistically significant mutational hotspot or a well-established critical functional domain of menin. The Cancer Hotspots analysis confirms this residue is not significant. Details ▾Hide ▴

Evidence considered

Cancer Hotspots: residue 145 not statistically significant
no known critical domain at this position.

PM2 PM2 is not met: the variant is common in population databases. gnomAD v2.1 reports an allele frequency of 2.84% (8021/282758 alleles) and v4.1 reports 3.54% (57090/1614046 alleles), both far exceeding the PM2 threshold of <0.1%. Details ▾Hide ▴

Evidence considered

gnomAD v2.1 AF=2.84% (far above PM2 <0.1% threshold)
gnomAD v4.1 AF=3.54%.

Sources

gnomad_v2 ↗gnomad_v4 ↗

PM6 PM6 is not met: no assumed de novo occurrence (parental status unconfirmed) has been reported for this variant in any available source. Details ▾Hide ▴

Evidence considered

No assumed de novo data found.

PP1 PP1 is not met: no cosegregation data with disease has been reported for this variant in affected families. Details ▾Hide ▴

Evidence considered

No segregation studies identified for c.435C>T.

Still missing

No family cosegregation data available.

PP3 PP3 is not met: no in silico tools predict a damaging effect. SpliceAI predicts no splice impact (max delta = 0.00). REVEL and BayesDel scores are not available for this variant, and no HCI prior probability is assigned to MEN1. Details ▾Hide ▴

Evidence considered

SpliceAI max delta = 0.00 (no predicted splice impact)
REVEL/BayesDel not available
HCI prior not supported for MEN1.

Still missing

REVEL and BayesDel scores unavailable for this variant.

Sources

spliceai ↗

PP4 PP4 is not met: no patient-specific phenotype or family history data are available to assess specificity for MEN1-related disease. Details ▾Hide ▴

Evidence considered

No clinical phenotype data linked to this variant.

Still missing

No individual patient phenotype data available.

PP5 PP5 is not met: no reputable source has reported this variant as pathogenic. ClinVar classifies it as Benign (18 clinical laboratories; ClinVar ID 96252). Details ▾Hide ▴

Evidence considered

ClinVar classification: Benign (18 clinical laboratories). No source reports this variant as pathogenic.

Sources

clinvar ↗

BS3 BS3 is not met: no well-established functional studies specifically evaluating NM_000244.3:c.435C>T have been published. While in silico tools predict no splice impact, this constitutes computational rather than functional evidence. Details ▾Hide ▴

Evidence considered

No dedicated functional assay data available for c.435C>T.

Still missing

No experimental functional studies confirming no effect on splicing or protein function.

BS4 BS4 is not met: no family studies demonstrating lack of cosegregation with MEN1-related disease have been reported for this variant. Details ▾Hide ▴

Evidence considered

No segregation data available.

Still missing

No family cosegregation studies evaluating c.435C>T.

BP5 BP5 is not met: no evidence that this variant has been observed in a case where an alternate molecular basis for disease was identified. Details ▾Hide ▴

Evidence considered

No cases with an alternate molecular diagnosis and c.435C>T identified.

PS5 PS5 is not met: no evidence that this variant has been detected in trans with a pathogenic variant for a recessive disorder. Details ▾Hide ▴

Evidence considered

No trans-phase observations with pathogenic variants in a recessive disease context.

Not applicable · 4· recorded as not applicable Show reasons ▾Hide reasons ▴

PVS1 N/APVS1 is not applicable: NM_000244.3:c.435C>T is a synonymous variant (p.Ser145=) that does not fall into any default null-variant bucket (nonsense, frameshift, or canonical ±1,2 splice consensus). The ClinGen SVI PVS1 framework (PMC6185798) confirms this variant is not eligible for generic PVS1 scoring. Details ▾Hide ▴

Evidence considered

Synonymous variant
no predicted null effect on protein.

Sources

pvs1_generic_framework ↗

PM5 N/APM5 is not applicable: this is a synonymous variant (p.Ser145=) with no missense change at the same residue. The pm5_candidates module confirmed no same-residue missense comparators could be identified. Details ▾Hide ▴

Evidence considered

Synonymous variant
no amino acid change to compare at codon 145.

PP2 N/APP2 is not applicable: this criterion applies to missense variants in genes with a low rate of benign missense variation. NM_000244.3:c.435C>T is a synonymous variant, not a missense change. Details ▾Hide ▴

Evidence considered

Synonymous variant
PP2 is specific to missense variants.

BP1 N/ABP1 is not applicable: this criterion applies to missense variants in genes where primarily truncating variants cause disease. NM_000244.3:c.435C>T is a synonymous variant, not a missense change. Details ▾Hide ▴

Evidence considered

Synonymous variant
BP1 is specific to missense variants.

Identifiers

Gene: MEN1
Transcript: NM_000244.3
Coding (HGVS c.): NM_000244.3:c.435C>T
Protein (HGVS p.): NP_000235.2:p.(Ser145=)
GRCh38: chr11:64809675 G>A
GRCh37: chr11:64577147 G>A
COSMIC: COSV56341605

Gene diagram

Every interpreted variant in MEN1, mapped onto the exon structure of NM_000244.3. Select a row to find it on the plot.

MEN1NM_000244.3

Fetching transcript structure from UCSC…

Exons

—

Transcript span

—

Strand

—

Variants mapped

—

Source

UCSC ncbiRefSeqCurated

All variants in MEN1 — Select a row to find it on the plot; use the link to open its page.

	Protein	Location	Classification	Link

gnomAD v4.1 57,090 / 1,614,046 alleles AF 0.0354 · 1240 homozygotes · FAF 0.0413

gnomAD v2.1 8,021 / 282,758 alleles AF 0.0284 · 189 homozygotes · FAF 0.0423

gnomAD-Canada v1.0 0 / 0 alleles AF 0 · 0 homozygotes · FAF 0

By genetic ancestry

gnomAD v4.1

AF 0.035 · 57090 / 1,614,046 alleles · 1240 hom · FAF 0.041

European (Finnish)4082 / 64,030	0.064142 hom
European (non-Finnish)49109 / 1,179,924	0.0421049 hom
Amish37 / 912	0.0411 hom
Remaining individuals1751 / 62,498	0.02836 hom
Middle Eastern75 / 6,062	0.0123 hom
Admixed American614 / 60,020	0.015 hom
South Asian694 / 91,084	0.00762 hom
Ashkenazi Jewish207 / 29,604	0.0072 hom
African/African American517 / 75,036	0.0069
East Asian4 / 44,876	8.9e-05

gnomAD v2.1

AF 0.028 · 8021 / 282,758 alleles · 189 hom · FAF 0.042

European (Finnish)1606 / 25,120	0.06463 hom
European (non-Finnish)5315 / 129,094	0.041110 hom
Remaining individuals233 / 7,218	0.0327 hom
Admixed American376 / 35,424	0.0116 hom
Ashkenazi Jewish81 / 10,368	0.00782 hom
South Asian234 / 30,614	0.00761 hom
African/African American173 / 24,968	0.0069
East Asian3 / 19,952	0.00015

gnomAD-Canada

AF 0 · 0 / 0 alleles · 0 hom

Statements

gnomAD v4.1

This variant is present in gnomAD v4.1 (AF= 0.0353707; MAF= 3.53707%, 57090/1614046 alleles, homozygotes = 1240) and has highest observed frequency in the European (Finnish) population (AF= 0.0637514; MAF= 6.37514%, 4082/64030 alleles, homozygotes = 142); grpmax FAF= 0.0413118.

gnomAD v2.1

Open the gnomAD-Canada detail page →

SpliceAI and Pangolin

Pangolin splice lossmagnitude shown

-0.050

Pangolin splice gain

0.050

Other predictors

REVEL: Not available
BayesDel: Not available

How the predictions were used

Evidence considered

SpliceAI max delta = 0.00
predicting no splice site creation or disruption.

Still missing

REVEL and BayesDel scores not available
conservation data not assessed.

Sources

spliceai ↗

Evidence considered

Synonymous variant with no amino acid change (p.Ser145=)
SpliceAI max delta = 0.00
no predicted alteration to splice consensus or creation of a new splice site

Still missing

Nucleotide conservation data at c.435 not directly assessed.

Sources

spliceai ↗

Evidence considered

SpliceAI max delta = 0.00 (no predicted splice impact)
REVEL/BayesDel not available
HCI prior not supported for MEN1.

Still missing

REVEL and BayesDel scores unavailable for this variant.

Sources

spliceai ↗

Statement

In silico

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

9 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

Germline mutations in the multiple endocrine neoplasia type 1 gene: evidence for frequent splicing defects.

No paper-specific finding is recorded.

PMID 10090472 ↗
Complete sequencing and messenger ribonucleic acid expression analysis of the MEN I gene in adrenal cancer.

No paper-specific finding is recorded.

PMID 10634422 ↗
Familial hypercalcemia and hypercalciuria caused by a novel mutation in the cytoplasmic tail of the calcium receptor.

No paper-specific finding is recorded.

PMID 10843194 ↗
Familial isolated hyperparathyroidism: clinical and genetic characteristics of 36 kindreds.

No paper-specific finding is recorded.

PMID 11807402 ↗
Clinical testing for mutations in the MEN1 gene in Sweden: a report on 200 unrelated cases.

No paper-specific finding is recorded.

PMID 17623761 ↗
MEN1 gene mutations in Hungarian patients with multiple endocrine neoplasia type 1.

No paper-specific finding is recorded.

PMID 17953629 ↗
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 ↗
Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

No paper-specific finding is recorded.

PMID 28492532 ↗

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

gnomAD v4.1 57,090 / 1,614,046 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 18 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

ClinVar

This variant has been reported in ClinVar as Benign (18 clinical laboratories). (ClinVarID = 96252)

In silico

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

Functional

OncoKB identified curated literature and non-variant-specific oncogenicity context for review; listed oncogenicity label: Unknown Oncogenic Effect.

Somatic

This variant does not lie in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV56341605, n = 2 times).

Cancer Hotspots

This variant does not lie in a statistically significant hotspot.