ClinVar Miner

Submissions for variant NM_000287.4(PEX6):c.1387A>G (p.Thr463Ala)

gnomAD frequency: 0.00008  dbSNP: rs182308788
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000358540 SCV000463348 uncertain significance Peroxisome biogenesis disorder 4A (Zellweger) 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Labcorp Genetics (formerly Invitae), Labcorp RCV001245260 SCV001418535 uncertain significance Peroxisome biogenesis disorder 2022-11-03 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 463 of the PEX6 protein (p.Thr463Ala). This variant is present in population databases (rs182308788, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with PEX6-related conditions. ClinVar contains an entry for this variant (Variation ID: 356796). 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 PEX6 protein function. 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 RCV004549812 SCV004118468 uncertain significance PEX6-related disorder 2023-02-14 criteria provided, single submitter clinical testing The PEX6 c.1387A>G variant is predicted to result in the amino acid substitution p.Thr463Ala. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.039% of alleles in individuals of Ashkenazi Jewish descent in gnomAD (http://gnomad.broadinstitute.org/variant/6-42936704-T-C). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Natera, Inc. RCV001828346 SCV002077318 uncertain significance Zellweger spectrum disorders 2020-01-22 no assertion criteria provided clinical testing

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