chr11-64804776-G-A
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 1P and 11B. PP2BP4_ModerateBP6BS1BS2
The NM_001370259.2(MEN1):c.1391C>T(p.Ala464Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000313 in 1,596,758 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001370259.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MEN1 | NM_001370259.2 | c.1391C>T | p.Ala464Val | missense_variant | Exon 10 of 10 | ENST00000450708.7 | NP_001357188.2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152164Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000664 AC: 15AN: 225766Hom.: 0 AF XY: 0.0000877 AC XY: 11AN XY: 125486
GnomAD4 exome AF: 0.0000339 AC: 49AN: 1444594Hom.: 0 Cov.: 43 AF XY: 0.0000473 AC XY: 34AN XY: 718830
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152164Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74330
ClinVar
Submissions by phenotype
Multiple endocrine neoplasia, type 1 Benign:2
- -
This variant is considered likely benign. This variant has been observed at a population frequency that is significantly greater than expected given the associated disease prevalence and penetrance. -
not provided Uncertain:1
The MEN1 c.1391C>T; p.Ala464Val variant (rs778728934), to our knowledge, is not reported in the medical literature. The variant is listed in the ClinVar database (Variation ID: 403807) and is reported in the South Asian population with an allele frequency of 0.05% (14/30252 alleles) in the Genome Aggregation Database. The alanine at codon 464 is moderately conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is tolerated. Due to limited information, the clinical significance of the p.Ala464Val variant is uncertain at this time. -
Hereditary cancer-predisposing syndrome Benign:1
This alteration is classified as 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at