rs779589005
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 3P and 7B. PM5PP2BP4_ModerateBP6BS2
The NM_001370259.2(MEN1):c.1399G>A(p.Ala467Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000626 in 1,596,488 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A467S) has been classified as Uncertain significance.
Frequency
Consequence
NM_001370259.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MEN1 | NM_001370259.2 | c.1399G>A | p.Ala467Thr | missense_variant | 10/10 | ENST00000450708.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MEN1 | ENST00000450708.7 | c.1399G>A | p.Ala467Thr | missense_variant | 10/10 | 5 | NM_001370259.2 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152186Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000178 AC: 4AN: 224660Hom.: 0 AF XY: 0.00000799 AC XY: 1AN XY: 125084
GnomAD4 exome AF: 0.00000554 AC: 8AN: 1444302Hom.: 0 Cov.: 43 AF XY: 0.00000417 AC XY: 3AN XY: 718716
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152186Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0AN XY: 74340
ClinVar
Submissions by phenotype
Multiple endocrine neoplasia, type 1 Uncertain:2Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Mar 19, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Jun 26, 2023 | This missense variant replaces alanine with threonine at codon 467 of the MEN1 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with MEN1-related disorders in the literature. This variant has been identified in 5/255980 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 16, 2023 | - - |
Hereditary cancer-predisposing syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 27, 2023 | 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