Submissions for variant NM_000512.5(GALNS):c.1376C>T (p.Ala459Val)

gnomAD frequency: 0.03559  dbSNP: rs114703967

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000535194	SCV000399627	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000535194	SCV000629964	benign	Mucopolysaccharidosis, MPS-IV-A	2024-01-31	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000780273	SCV000917404	benign	not specified	2017-10-30	criteria provided, single submitter	clinical testing	Variant summary: The GALNS c.1376C>T (p.Ala459Val) variant involves the alteration of a non-conserved nucleotide and 3/4 in silico tools predict a benign outcome for this variant (SNPsandGO not captured due to low reliability index). This variant was found in 2649/218538 control chromosomes (gnomAD), predominantly observed in the African subpopulation at a frequency of 0.119713 (2406/20098). This frequency is about 59 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, Bunge_1997, cites the variant of interest in an affected individual, who was homozygote for a pathogenic GALNS variant, G47R. In addition, multiple clinical diagnostic laboratories classified this variant as likely benign/benign. Taken together, this variant is classified as benign.
GeneDx	RCV000675529	SCV000976989	benign	not provided	2018-06-13	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.
Genome-Nilou Lab	RCV000535194	SCV002045050	benign	Mucopolysaccharidosis, MPS-IV-A	2021-11-07	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000675529	SCV005252575	benign	not provided		criteria provided, single submitter	not provided
Mayo Clinic Laboratories, Mayo Clinic	RCV000675529	SCV000801220	benign	not provided	2017-04-24	no assertion criteria provided	clinical testing