ClinVar Miner

Submissions for variant NM_001351132.2(PEX5):c.421T>G (p.Ser141Ala)

gnomAD frequency: 0.00006  dbSNP: rs200475014
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000591377 SCV000704790 uncertain significance not provided 2017-10-03 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV001109085 SCV001266393 uncertain significance Peroxisome biogenesis disorder 2A (Zellweger) 2017-04-28 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV001867954 SCV002118351 uncertain significance Peroxisome biogenesis disorder 2B 2022-10-17 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 141 of the PEX5 protein (p.Ser141Ala). This variant is present in population databases (rs200475014, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with PEX5-related conditions. ClinVar contains an entry for this variant (Variation ID: 499350). 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 not expected to disrupt PEX5 protein function. Experimental studies have shown that this missense change affects PEX5 function (PMID: 26344566). 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.
PreventionGenetics, part of Exact Sciences RCV003409863 SCV004115361 uncertain significance PEX5-related disorder 2022-12-14 criteria provided, single submitter clinical testing The PEX5 c.421T>G variant is predicted to result in the amino acid substitution p.Ser141Ala. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.013% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/12-7344269-T-G). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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