chr11-64806312-G-C
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_001370259.2(MEN1):c.969C>G(p.Tyr323Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. Y323Y) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001370259.2 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MEN1 | NM_001370259.2 | c.969C>G | p.Tyr323Ter | stop_gained | 7/10 | ENST00000450708.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MEN1 | ENST00000450708.7 | c.969C>G | p.Tyr323Ter | stop_gained | 7/10 | 5 | NM_001370259.2 | P3 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome Cov.: 32
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Multiple endocrine neoplasia, type 1 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jun 29, 2019 | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in MEN1 are known to be pathogenic (PMID: 12112656, 17853334). A different variant (c.969C>A) giving rise to the same protein effect observed here (p.Tyr323*) has been reported in individuals affected with multiple endocrine neoplasia (PMID: 12791038, 22026581, 25309785). This variant has been reported in individuals affected with multiple endocrine neoplasia type 1 (PMID: 9215689). ClinVar contains an entry for this variant (Variation ID: 449058). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Tyr323*) in the MEN1 gene. It is expected to result in an absent or disrupted protein product. - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | May 12, 2022 | Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Also known as c.984C>G; p.(Y328*); This variant is associated with the following publications: (PMID: 25525159, 9215689, 9540988, 12791038, 15464422, 12807514) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at