ClinVar Miner

Submissions for variant NM_000466.3(PEX1):c.952G>A (p.Asp318Asn)

gnomAD frequency: 0.00004  dbSNP: rs754893068
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV001164202 SCV001326314 uncertain significance Peroxisome biogenesis disorder 1A (Zellweger) 2018-01-13 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.
Invitae RCV002559575 SCV003483627 uncertain significance Zellweger spectrum disorders 2022-09-13 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 318 of the PEX1 protein (p.Asp318Asn). This variant is present in population databases (rs754893068, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with PEX1-related conditions. ClinVar contains an entry for this variant (Variation ID: 911637). 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 PEX1 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.
Ambry Genetics RCV002559574 SCV003613188 uncertain significance Inborn genetic diseases 2022-02-24 criteria provided, single submitter clinical testing The c.952G>A (p.D318N) alteration is located in exon 5 (coding exon 5) of the PEX1 gene. This alteration results from a G to A substitution at nucleotide position 952, causing the aspartic acid (D) at amino acid position 318 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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