Submissions for variant NM_000512.5(GALNS):c.634-20C>T

gnomAD frequency: 0.08794  dbSNP: rs17603837

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000079040	SCV000110909	benign	not specified	2017-01-26	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000079040	SCV000304616	benign	not specified		criteria provided, single submitter	clinical testing
GeneDx	RCV000079040	SCV000728478	benign	not specified	2017-06-16	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.
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000601822	SCV000745325	benign	Mucopolysaccharidosis, MPS-IV-A	2015-09-21	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000079040	SCV001361773	benign	not specified	2019-02-15	criteria provided, single submitter	clinical testing	Variant summary: GALNS c.634-20C>T alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. The variant allele was found at a frequency of 0.096 in 276718 control chromosomes in the gnomAD database, including 1472 homozygotes. The observed variant frequency is approximately 47-folds higher than the estimated maximal expected allele frequency for a pathogenic variant in GALNS causing Mucopolysaccharidosis Type IVA (Morquio Syndrome A) phenotype (0.002), strongly suggesting that the variant is benign. Four ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as benign. Based on the evidence outlined above, the variant was classified as benign.
Invitae	RCV000601822	SCV001726864	benign	Mucopolysaccharidosis, MPS-IV-A	2024-02-01	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000601822	SCV002045065	benign	Mucopolysaccharidosis, MPS-IV-A	2021-11-07	criteria provided, single submitter	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000601822	SCV000733546	benign	Mucopolysaccharidosis, MPS-IV-A		no assertion criteria provided	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000675544	SCV000801235	benign	not provided	2015-10-23	no assertion criteria provided	clinical testing