Submissions for variant NM_000512.5(GALNS):c.1431G>A (p.Glu477=)

gnomAD frequency: 0.40780  dbSNP: rs2303271

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000079026	SCV000110895	benign	not specified	2017-01-26	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000079026	SCV000304608	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000604885	SCV000399625	benign	Mucopolysaccharidosis, MPS-IV-A	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.
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000604885	SCV000745323	benign	Mucopolysaccharidosis, MPS-IV-A	2015-09-21	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000079026	SCV000917406	benign	not specified	2017-10-30	criteria provided, single submitter	clinical testing	Variant summary: The GALNS c.1431G>A (p.Glu477Glu) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a benign outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. This variant was found in 91177/224468 control chromosomes (882 homozygotes) at a frequency of 0.4061915, which is approximately 199 times the estimated maximal expected allele frequency of a pathogenic GALNS variant (0.0020412), strong evidence that this variant is a benign polymorphism. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign. Taken together, this variant is classified as benign.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000604885	SCV001732798	benign	Mucopolysaccharidosis, MPS-IV-A	2024-02-01	criteria provided, single submitter	clinical testing
GeneDx	RCV000675527	SCV001759177	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000604885	SCV001933715	benign	Mucopolysaccharidosis, MPS-IV-A	2021-08-10	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000675527	SCV005252573	benign	not provided		criteria provided, single submitter	not provided
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000604885	SCV000733544	benign	Mucopolysaccharidosis, MPS-IV-A		no assertion criteria provided	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000675527	SCV000801218	benign	not provided	2015-10-22	no assertion criteria provided	clinical testing