9-137163606-G-A
Variant summary
Our verdict is Pathogenic. Variant got 14 ACMG points: 15P and 1B. PM1PM2PM5PP2PP5_Very_StrongBP4
The NM_007327.4(GRIN1):c.2381G>A(p.Arg794Gln) 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 benign outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R794G) has been classified as Likely pathogenic.
Frequency
Consequence
NM_007327.4 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 |
---|---|---|---|---|---|---|---|
GRIN1 | NM_007327.4 | c.2381G>A | p.Arg794Gln | missense_variant | 17/20 | ENST00000371561.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GRIN1 | ENST00000371561.8 | c.2381G>A | p.Arg794Gln | missense_variant | 17/20 | 1 | NM_007327.4 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome Cov.: 32
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Intellectual disability, autosomal dominant 8 Pathogenic:3
Likely pathogenic, no assertion criteria provided | clinical testing | Molecular Genetics Laboratory, BC Children's and BC Women's Hospitals | Feb 02, 2016 | - - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Dec 28, 2016 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Feb 25, 2022 | For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects GRIN1 function (PMID: 29365063). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt GRIN1 protein function. ClinVar contains an entry for this variant (Variation ID: 435376). This missense change has been observed in individual(s) with clinical features of GRIN1-related conditions (PMID: 29365063). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 794 of the GRIN1 protein (p.Arg794Gln). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at