chrX-107645232-C-T
Variant summary
Our verdict is Pathogenic. Variant got 13 ACMG points: 13P and 0B. PM2PP2PP3_ModeratePP5_Very_Strong
The NM_002764.4(PRPS1):c.586C>T(p.Arg196Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. R196Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_002764.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRPS1 | NM_002764.4 | c.586C>T | p.Arg196Trp | missense_variant | 5/7 | ENST00000372435.10 | |
PRPS1 | NM_001204402.2 | c.-27C>T | 5_prime_UTR_variant | 2/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRPS1 | ENST00000372435.10 | c.586C>T | p.Arg196Trp | missense_variant | 5/7 | 1 | NM_002764.4 | P1 |
Frequencies
GnomAD3 genomes Cov.: 23
GnomAD4 exome Cov.: 31
GnomAD4 genome Cov.: 23
ClinVar
Submissions by phenotype
Charcot-Marie-Tooth Neuropathy X Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jul 13, 2022 | For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 446162). This missense change has been observed in individuals with clinical features of PRPS1-related conditions (PMID: 24961627, 28967191, 32781272; Invitae). 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 arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 196 of the PRPS1 protein (p.Arg196Trp). - |
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Dec 07, 2022 | Not observed in large population cohorts (gnomAD); 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: 28967191, 24961627, 32650483, 32781272) - |
Retinal dystrophy Pathogenic:1
Likely pathogenic, no assertion criteria provided | research | Hardcastle Lab, UCL Institute of Ophthalmology | Jan 01, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at