Submissions for variant NM_002618.4(PEX13):c.89T>C (p.Phe30Ser)

dbSNP: rs771610641

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000592064	SCV000706672	uncertain significance	not provided	2017-08-15	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000765692	SCV000897034	uncertain significance	Peroxisome biogenesis disorder 11A (Zellweger); Peroxisome biogenesis disorder 11B	2018-10-31	criteria provided, single submitter	clinical testing
Invitae	RCV001059125	SCV001223734	uncertain significance	Peroxisome biogenesis disorder 11A (Zellweger)	2022-10-17	criteria provided, single submitter	clinical testing	This sequence change replaces phenylalanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 30 of the PEX13 protein (p.Phe30Ser). This variant is present in population databases (rs771610641, gnomAD 0.1%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with PEX13-related conditions. ClinVar contains an entry for this variant (Variation ID: 500639). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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.
Illumina Laboratory Services, Illumina	RCV001059125	SCV001300709	uncertain significance	Peroxisome biogenesis disorder 11A (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.
Ambry Genetics	RCV002531070	SCV003677557	uncertain significance	Inborn genetic diseases	2021-06-11	criteria provided, single submitter	clinical testing	The c.89T>C (p.F30S) alteration is located in exon 1 (coding exon 1) of the PEX13 gene. This alteration results from a T to C substitution at nucleotide position 89, causing the phenylalanine (F) at amino acid position 30 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences	RCV003927928	SCV004743144	uncertain significance	PEX13-related condition	2024-01-19	criteria provided, single submitter	clinical testing	The PEX13 c.89T>C variant is predicted to result in the amino acid substitution p.Phe30Ser. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.091% of alleles in individuals of European (Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.