Submissions for variant NM_000287.4(PEX6):c.399G>T (p.Val133=)

gnomAD frequency: 0.40569  dbSNP: rs9462858

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000078576	SCV000110432	benign	not specified	2018-07-10	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000078576	SCV000303470	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000288691	SCV000463361	benign	Peroxisome biogenesis disorder 4A (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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000588719	SCV000696489	benign	not provided	2016-10-10	criteria provided, single submitter	clinical testing	Variant summary: The PEX6 c.399G>T (p.Val133Val) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. 5/5 splice prediction tools predict the variant not to have a significant impact on splicing. This variant was found in 5625/12518 control chromosomes (1242 homozygotes) at a frequency of 0.4493529, which greatly exceeds the estimated maximal expected allele frequency of a pathogenic PEX6 variant (0.0019365), suggesting this variant is likely a benign polymorphism. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign. Taken together, this variant is classified as benign.
GeneDx	RCV000588719	SCV000968185	benign	not provided	2018-06-13	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001409911	SCV001611946	likely benign	Peroxisome biogenesis disorder	2025-02-04	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001543847	SCV001762724	benign	Heimler syndrome 2	2021-07-10	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000288691	SCV001762725	benign	Peroxisome biogenesis disorder 4A (Zellweger)	2021-07-10	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001543848	SCV001762726	benign	Peroxisome biogenesis disorder 4B	2021-07-10	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000588719	SCV005223810	likely benign	not provided		criteria provided, single submitter	not provided
Mayo Clinic Laboratories, Mayo Clinic	RCV000588719	SCV000801840	benign	not provided	2015-10-21	no assertion criteria provided	clinical testing
Natera, Inc.	RCV001276625	SCV001463077	benign	Zellweger spectrum disorders	2020-09-16	no assertion criteria provided	clinical testing