11-64804418-C-G
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6BP7
The NM_001370259.2(MEN1):c.1749G>C(p.Ser583=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,862 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). Synonymous variant affecting the same amino acid position (i.e. S583S) has been classified as Likely benign.
Frequency
Consequence
NM_001370259.2 synonymous
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.1749G>C | p.Ser583= | synonymous_variant | 10/10 | ENST00000450708.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MEN1 | ENST00000450708.7 | c.1749G>C | p.Ser583= | synonymous_variant | 10/10 | 5 | NM_001370259.2 | P3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251438Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135906
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461862Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3AN XY: 727230
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Multiple endocrine neoplasia, type 1 Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Feb 24, 2023 | This variant is located in the MEN1 protein. 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 2/251438 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. - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | May 19, 2022 | - - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 25, 2019 | 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at