Submissions for variant NM_004813.4(PEX16):c.204G>T (p.Glu68Asp)

gnomAD frequency: 0.00192  dbSNP: rs149348130

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000177215	SCV000229053	benign	not specified	2015-11-23	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000358606	SCV000372069	uncertain significance	Peroxisome biogenesis disorder 8A (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.
GeneDx	RCV000766831	SCV000618593	uncertain significance	not provided	2017-06-29	criteria provided, single submitter	clinical testing	The E68D variant in the PEX16 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The E68D variant is observed in 68/10,406 (0.65%) alleles from individuals of African background in the ExAC dataset (Lek et al., 2016). This substitution occurs at a position that is conserved in mammals. However, the E68D variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret E68D as a variant of uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001079444	SCV001106845	likely benign	Peroxisome biogenesis disorder	2024-01-31	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003955053	SCV004772689	likely benign	PEX16-related disorder	2020-05-18	no assertion criteria provided	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).