Submissions for variant NM_000046.5(ARSB):c.1213+6T>C (rs1554074118)

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	RCV000677466	SCV000802973	pathogenic	Mucopolysaccharidosis type 6	2018-01-01	criteria provided, single submitter	curation	Splicing variant in NON-canonical site (PVS1); in vitro functional studies supportive of a damaging effect on the gene product (low to no ARSB activity in homozygotes; PS3); Absent from GnomAD (PM2);
Invitae	RCV000677466	SCV001514925	uncertain significance	Mucopolysaccharidosis type 6	2020-10-26	criteria provided, single submitter	clinical testing	This sequence change falls in intron 6 of the ARSB gene. It does not directly change the encoded amino acid sequence of the ARSB protein. It affects a nucleotide within the consensus splice site of the intron. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with mucopolysaccharidosis type VI (PMID: 30809705). ClinVar contains an entry for this variant (Variation ID: 559692). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.