rs104893788
Variant summary
Our verdict is Pathogenic. Variant got 16 ACMG points: 16P and 0B. PM1PM5PP3_StrongPP5_Very_Strong
The NM_000539.3(RHO):c.341G>A(p.Gly114Asp) variant causes a missense change involving the alteration of a conserved nucleotide. 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 Pathogenic (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G114V) has been classified as Pathogenic.
Frequency
Consequence
NM_000539.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RHO | NM_000539.3 | c.341G>A | p.Gly114Asp | missense_variant | 1/5 | ENST00000296271.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RHO | ENST00000296271.4 | c.341G>A | p.Gly114Asp | missense_variant | 1/5 | 1 | NM_000539.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1460842Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 726586
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Retinitis pigmentosa 4 Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Centre for Genomic Medicine, Manchester, Central Manchester University Hospitals | Sep 01, 2020 | - - |
Pathogenic, no assertion criteria provided | literature only | OMIM | May 15, 1994 | - - |
not provided Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Mar 09, 2022 | For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects RHO function (PMID: 30977563). 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 RHO protein function. ClinVar contains an entry for this variant (Variation ID: 13048). This missense change has been observed in individual(s) with autosomal dominant retinitis pigmentosa (PMID: 8088850). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 114 of the RHO protein (p.Gly114Asp). - |
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Aug 16, 2022 | Published functional studies demonstrate a damaging effect on cellular localization (Behnen et al., 2018); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 21094163, 30977563, 12646201, 8088850, 19414246, 26986070, 28559085, 7760863, 30240733) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at