Genetic Information

Gene & Transcript Details

Gene
MEN1
Transcript
NM_000244.3 MANE Select
Total Exons
—
Reference Sequence
NC_000011.9
Alternative Transcripts
IDStatusDetails
NM_000244.3 Alternative 2785 nt | 111–1958
NM_000244.4 Alternative 2746 nt | 81–1928
NM_000244.2 Alternative 2787 nt | 111–1958

Variant Details

HGVS Notation
NM_000244.3:c.1311G>A
Protein Change
L437=
Location
Exon 9 (Exon 9 of )
9
5'Exon Structure3'
Functional Consequence
Loss of Function
Alternate Identifiers
—

Clinical & Population Data

Population Frequency

gnomAD
Global Frequency
0.112 in 100,000
Extremely Rare
ACMG Criteria Applied None

ClinVar

Open
Classification
Uncertain Significance (VUS)
3 publications
Publications List
PMID: 16563611

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

Clinical Statement

"This variant has been reported in ClinVar as Likely benign (10 clinical laboratories) and as Benign (7 clinical laboratories) and as Uncertain significance (1 clinical laboratories)."

COSMIC Somatic Evidence

Open
COSMIC ID
Recurrence
0 occurrences
PM1 Criteria
Not Applied
COSMIC Database Preview
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Functional Impact & Domains

Functional Domain

Hotspot Status
Not a hotspot
Domain Summary
This variant is not located in a mutational hotspot or critical domain.
Related Variants in This Domain
No evidence of other pathogenic variants at this position in gene MEN1.

Functional Studies & Therapeutic Relevance

Functional Summary

Error in OpenAI Consolidation. OncoKB: MEN1L437=MEN1L437=SomaticNCBI Gene:4221|Show additional gene information Variant OverviewMEN1, a transcriptional repressor, is altered by mutation and deletion in various cancer types, including parathyroid and endocrine cancers.This is a synonymous mutation and is not annotated by OncoKB. JAX-CKB: No results found

Database Previews
OncoKB
OncoKB Preview
JAX-CKB
JAX-CKB Preview

Click on previews to view full database entries. External databases may require institutional access.

Computational Analysis

Pathogenicity Predictions

SpliceAI
Predictor Consensus
Mixed/VUS
PP3 Applied
No
REVEL Score
0.0
Threshold: ≥0.75 = PP3 applied

SpliceAI Scores

Window: ±500bp
Effect Type Score Position
- Acceptor Loss (AL) 0.0 110 bp
- Donor Loss (DL) 0.01 -54 bp
+ Acceptor Gain (AG) 0.0 80 bp
+ Donor Gain (DG) 0.08 -3 bp
High impact (≥0.5) Medium impact (0.2-0.49) Low impact (<0.2)

VCEP Guidelines

Applied ACMG/AMP Criteria (VCEP Specific)

Filter Criteria:
BP4

BP4 (Unknown (Pre-LLM))

From pre-LLM assessment (LLM Failed)