rs1114167493
Variant summary
Our verdict is Pathogenic. Variant got 15 ACMG points: 15P and 0B. PS1PM1PM2PP2PP3_StrongPP5_Moderate
The NM_001370259.2(MEN1):c.841G>A(p.Gly281Arg) variant causes a missense change. 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 Likely pathogenic (★). Another nucleotide change resulting in same amino acid change has been previously reported as Pathogenicin Lovd. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G281E) has been classified as Uncertain significance.
Frequency
Consequence
NM_001370259.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 15 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MEN1 | NM_001370259.2 | c.841G>A | p.Gly281Arg | missense_variant | 6/10 | ENST00000450708.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MEN1 | ENST00000450708.7 | c.841G>A | p.Gly281Arg | missense_variant | 6/10 | 5 | NM_001370259.2 | P3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome Cov.: 33
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 10, 2014 | The p.G281R variant (also known as c.841G>A), located in coding exon 5 of the MEN1 gene, results from a G to A substitution at nucleotide position 841. The glycine at codon 281 is replaced by arginine, an amino acid with dissimilar properties.This alteration has been reported in one individual with a clinical diagnosis of MEN1 (Crepin M et al. Electrophoresis. 2003 Jan;24(1-2):26-33).A similar alteration, c.841G>C, has been reported in one family with hyperparathyroidism, a pituitary adenoma, and CNS tumors (Wautot V et al. Hum Mutat. 2002 Jul;20(1):35-47).This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. To date, this alteration has been detected with an allele frequency of approximately 0.10% (greater than 1000 alleles tested) in our clinical cohort (includes this individual). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be probably damaging and deleterious by PolyPhen and SIFT in silico analyses, respectively.Based on the majority of available evidence to date, this variant is likely to be pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at