ClinVar Miner

Submissions for variant NM_181882.3(PRX):c.500G>A (p.Arg167His)

dbSNP: rs757322355
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000816878 SCV000957405 uncertain significance Charcot-Marie-Tooth disease type 4 2021-11-04 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 167 of the PRX protein (p.Arg167His). This variant is present in population databases (rs757322355, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with PRX-related conditions. ClinVar contains an entry for this variant (Variation ID: 659819). 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: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Molecular Genetics Laboratory, London Health Sciences Centre RCV001173952 SCV001337071 uncertain significance Charcot-Marie-Tooth disease criteria provided, single submitter clinical testing
Ambry Genetics RCV002336690 SCV002641411 uncertain significance Inborn genetic diseases 2021-11-11 criteria provided, single submitter clinical testing The p.R167H variant (also known as c.500G>A), located in coding exon 4 of the PRX gene, results from a G to A substitution at nucleotide position 500. The arginine at codon 167 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003994129 SCV004813439 uncertain significance not specified 2024-02-07 criteria provided, single submitter clinical testing Variant summary: PRX c.500G>A (p.Arg167His) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 1.8e-05 in 225716 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.500G>A in individuals affected with PRX-Related Disorders and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 659819). Based on the evidence outlined above, the variant was classified as uncertain significance.

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