Submissions for variant NM_000512.5(GALNS):c.846C>T (p.Phe282=)

gnomAD frequency: 0.03726  dbSNP: rs35232749

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000079045	SCV000110914	benign	not specified	2012-11-12	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000079045	SCV000304621	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000350630	SCV000399641	benign	Mucopolysaccharidosis, MPS-IV-A	2018-01-12	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.
GeneDx	RCV000675537	SCV000977253	benign	not provided	2018-05-01	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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000079045	SCV001361771	benign	not specified	2019-02-15	criteria provided, single submitter	clinical testing	Variant summary: GALNS c.846C>T alters a non-conserved nucleotide resulting in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.062 in 84726 control chromosomes in the gnomAD database, including 143 homozygotes. The observed variant frequency is approximately 30-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. Two ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as likely benign/benign. Based on the evidence outlined above, the variant was classified as benign.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000350630	SCV001718521	benign	Mucopolysaccharidosis, MPS-IV-A	2024-02-01	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000350630	SCV002045060	benign	Mucopolysaccharidosis, MPS-IV-A	2021-11-07	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000675537	SCV005252594	benign	not provided		criteria provided, single submitter	not provided
Mayo Clinic Laboratories, Mayo Clinic	RCV000675537	SCV000801228	benign	not provided	2015-10-22	no assertion criteria provided	clinical testing