Submissions for variant NM_000512.5(GALNS):c.199C>A (p.Leu67Met)

gnomAD frequency: 0.10099  dbSNP: rs11862754

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000079030	SCV000110899	benign	not specified	2013-11-14	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000079030	SCV000304610	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000560366	SCV000399659	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	RCV000079030	SCV000513100	benign	not specified	2015-05-20	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000560366	SCV000629966	benign	Mucopolysaccharidosis, MPS-IV-A	2025-02-03	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000079030	SCV000917407	benign	not specified	2017-10-30	criteria provided, single submitter	clinical testing	Variant summary: The GALNS c.199C>A (p.Leu67Met) variant located in the Sulfatase, N-terminal (InterPro) involves the alteration of a conserved nucleotide and 5/5 in silico tools predict a benign outcome for this variant. This variant was found in 8588/274128 control chromosomes, predominantly observed in the African subpopulation at a frequency of 0.327481 (7722/23580). This frequency is about 160 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. A publication, Laradi_2006 found the variant of interest to co-occur with pathogenic GALNS variants. In addition, multiple clinical diagnostic laboratories classified this variant as benign. Taken together, this variant is classified as benign.
Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova	RCV000560366	SCV001547614	benign	Mucopolysaccharidosis, MPS-IV-A	2021-02-01	criteria provided, single submitter	curation	Allele frequency is >5% in gnomAD v2.1.1 (BA1); allele frequency is greater than expected for disorder (BS1_strong); multiple lines of computational evidence suggest no impact on gene or gene product (BP4_supporting)
Genome-Nilou Lab	RCV000560366	SCV002045075	benign	Mucopolysaccharidosis, MPS-IV-A	2021-11-07	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000675552	SCV005252621	benign	not provided		criteria provided, single submitter	not provided
Mayo Clinic Laboratories, Mayo Clinic	RCV000675552	SCV000801243	benign	not provided	2017-03-16	no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000675552	SCV001800156	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000079030	SCV001969787	benign	not specified		no assertion criteria provided	clinical testing