Submissions for variant NM_000512.5(GALNS):c.1413C>T (p.Val471=)

gnomAD frequency: 0.01159  dbSNP: rs73251084

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000079025	SCV000110894	benign	not specified	2013-11-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001078610	SCV000399626	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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000079025	SCV000917405	benign	not specified	2017-10-30	criteria provided, single submitter	clinical testing	Variant summary: The GALNS c.1413C>T (p.Val471Val) 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. ESE finder predicts that this variant may affect the binding sites for splicing enhancers. However, these predictions have yet to be confirmed by functional studies. This variant was found in 884/216186 control chromosomes, predominantly observed in the African subpopulation at a frequency of 0.041844 (827/19764). This frequency is about 20 times the estimated maximal expected allele frequency of a pathogenic GALNS variant (0.0020412), suggesting this is likely a benign polymorphism found primarily in the populations of African origin. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign/likely benign. The variant of interest has not, to our knowledge, been reported in affected individuals via publications; nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as benign.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001078610	SCV001116896	benign	Mucopolysaccharidosis, MPS-IV-A	2025-02-03	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001078610	SCV002045049	benign	Mucopolysaccharidosis, MPS-IV-A	2021-11-07	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000675528	SCV005252574	benign	not provided		criteria provided, single submitter	not provided
Mayo Clinic Laboratories, Mayo Clinic	RCV000675528	SCV000801219	likely benign	not provided	2017-05-01	no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003952496	SCV004778748	benign	GALNS-related disorder	2019-10-01	no assertion criteria provided	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).