Submissions for variant NM_000046.5(ARSB):c.175G>A (p.Asp59Asn)

dbSNP: rs1236509896

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova	RCV000677508	SCV000803018	uncertain significance	Mucopolysaccharidosis type 6	2018-01-01	criteria provided, single submitter	curation	Absent from GnomAD (PM2);
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003323680	SCV004030080	uncertain significance	not specified	2023-07-11	criteria provided, single submitter	clinical testing	Variant summary: ARSB c.175G>A (p.Asp59Asn) results in a conservative amino acid change located in the sulfatase, N-terminal domain (IPR000917) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 182070 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.175G>A has been reported in the literature in the heterozygous state in two Brazilian individuals affected with Mucopolysaccharidosis Type VI (Maroteaux-Lamy Syndrome) (Petry_2005, Horovitz_2015). These reports do not provide unequivocal conclusions about association of the variant with Mucopolysaccharidosis Type VI (Maroteaux-Lamy Syndrome). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 28649537, 16435196). One submitter has provided a clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.