Submissions for variant NM_000286.3(PEX12):c.102A>T (p.Arg34Ser)

gnomAD frequency: 0.00493  dbSNP: rs147530802

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000078560	SCV000110416	benign	not specified	2014-05-02	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000078560	SCV000540016	likely benign	not specified	2016-03-28	criteria provided, single submitter	clinical testing	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Benign by Emory 2014. Has been reported in 2 homozygous individuals of iranian origin, who presented with peroxisomal biogenesis disorder with mild clinical phenotype. Consanguinity in at least one of the families. (Zeharia 2007). Given the high frequency in ExAC, LB
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000514867	SCV000610365	benign	not provided	2017-09-18	criteria provided, single submitter	clinical testing
Invitae	RCV001082581	SCV001099586	benign	Peroxisome biogenesis disorder 3A (Zellweger)	2024-01-31	criteria provided, single submitter	clinical testing
Mendelics	RCV000989844	SCV001140435	benign	Peroxisome biogenesis disorder type 3B	2019-05-28	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001082581	SCV001284750	likely benign	Peroxisome biogenesis disorder 3A (Zellweger)	2017-04-27	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. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
GeneDx	RCV000514867	SCV001831033	benign	not provided	2020-12-09	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 26643206, 17534573, 15542397)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000078560	SCV002555864	benign	not specified	2022-06-14	criteria provided, single submitter	clinical testing	Variant summary: PEX12 c.102A>T (p.Arg34Ser) results in a non-conservative amino acid change located in the Pex, N-terminal domain (IPR006845) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0058 in 282832 control chromosomes in the gnomAD database, including 17 homozygotes. The observed variant frequency is approximately 4 fold of the estimated maximal expected allele frequency for a pathogenic variant in PEX12 causing Zellweger Syndrome (0.0016), strongly suggesting that the variant is benign. Six ClinVar submitters have assessed the variant since 2014: two classified the variant as likely benign and four as benign. Based on the evidence outlined above, the variant was classified as benign.
Fulgent Genetics, Fulgent Genetics	RCV002498379	SCV002808579	likely benign	Peroxisome biogenesis disorder type 3B; Peroxisome biogenesis disorder 3A (Zellweger)	2022-04-12	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000514867	SCV004144463	likely benign	not provided	2023-01-01	criteria provided, single submitter	clinical testing	PEX12: BS2
PreventionGenetics, part of Exact Sciences	RCV003982875	SCV004797104	likely benign	PEX12-related condition	2020-02-14	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000078560	SCV001927793	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000078560	SCV001973842	benign	not specified		no assertion criteria provided	clinical testing