rs28933394
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PM1PM2PM5PP3_StrongPP5_Very_Strong
The NM_000539.3(RHO):āc.173C>Gā(p.Thr58Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T58M) has been classified as Uncertain significance.
Frequency
Consequence
NM_000539.3 missense
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 |
---|---|---|---|---|---|---|---|
RHO | NM_000539.3 | c.173C>G | p.Thr58Arg | missense_variant | 1/5 | ENST00000296271.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RHO | ENST00000296271.4 | c.173C>G | p.Thr58Arg | missense_variant | 1/5 | 1 | NM_000539.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461888Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1AN XY: 727244
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Retinitis pigmentosa 4 Pathogenic:4
Likely pathogenic, criteria provided, single submitter | clinical testing | MGZ Medical Genetics Center | Feb 04, 2022 | - - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Oct 01, 1991 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Mendelics | May 28, 2019 | - - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Centre for Genomic Medicine, Manchester, Central Manchester University Hospitals | Sep 01, 2020 | - - |
not provided Pathogenic:2
Likely pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Aug 24, 2023 | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 2333895, 15823756, 21094163, 8486634, 1924344, 2215617, 36648560, 30977563, 32483926, 25408095, 32882181, 32795431, 31717845, 29847639, 33777460, 31908405, 1929926, 28981474, 32037395, 18385078, 1882937, 8328469) - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Dec 27, 2022 | For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects RHO function (PMID: 1924344). 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: 13016). This missense change has been observed in individuals with autosomal dominant retinitis pigmentosa (PMID: 2215617, 29847639). 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 threonine, which is neutral and polar, with arginine, which is basic and polar, at codon 58 of the RHO protein (p.Thr58Arg). - |
Retinal dystrophy Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Blueprint Genetics | Jul 29, 2019 | - - |
Likely pathogenic, criteria provided, single submitter | research | Dept Of Ophthalmology, Nagoya University | Oct 01, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at