rs1057519757
Variant summary
Our verdict is Pathogenic. Variant got 14 ACMG points: 14P and 0B. PS1PM1PM2PP2PP3_StrongPP5
The NM_181523.3(PIK3R1):c.1126G>A(p.Gly376Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 12/20 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely pathogenicin ClinVar.
Frequency
Consequence
NM_181523.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 14 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PIK3R1 | NM_181523.3 | c.1126G>A | p.Gly376Arg | missense_variant | 10/16 | ENST00000521381.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PIK3R1 | ENST00000521381.6 | c.1126G>A | p.Gly376Arg | missense_variant | 10/16 | 1 | NM_181523.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome Cov.: 29
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Neoplasm Pathogenic:1
Likely pathogenic, no assertion criteria provided | literature only | Database of Curated Mutations (DoCM) | Jul 14, 2015 | - - |
Vascular Malformations and Overgrowth Pathogenic:1
Pathogenic, no assertion criteria provided | research | Institute for Genomic Medicine (IGM) Clinical Laboratory, Nationwide Children's Hospital | Nov 08, 2020 | This alteration is both well-represented in cancer as identified in the COSMIC database with >=20 documented instances and also considered to occur in a statistically significant hotspot or region according to cancerhotspots.org database [PS_CANCER], is supported by well-established models demonstrating downstream impact of the variant on RNA structure, gene expression, or protein function [PS3], is of apparent somatic mosaic etiology with moderate supporting evidence including no discernible strand bias, in a region absent of repetition and sequence homology, with clean, high-quality reads, having a variant allele fraction < 3% [PS2_Mod], and is a missense variant in a gene that has a low rate of benign missense variation and in which missense variants are a common mechanism of disease [PP2]. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at