Submissions for variant NM_152419.3(HGSNAT):c.1542+4dup

dbSNP: rs1401818080

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001339990	SCV001533776	pathogenic	Mucopolysaccharidosis, MPS-III-C; Retinitis pigmentosa 73	2023-12-21	criteria provided, single submitter	clinical testing	This sequence change falls in intron 15 of the HGSNAT gene. It does not directly change the encoded amino acid sequence of the HGSNAT protein. RNA analysis indicates that this variant induces altered splicing and likely results in a shortened protein product. This variant is present in population databases (no rsID available, gnomAD 0.002%). This variant has been observed in individual(s) with mucopolysaccharidosis type IIIC (PMID: 19479962, 25491247). ClinVar contains an entry for this variant (Variation ID: 438150). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant results in skipping of exon 15, but is expected to preserve the integrity of the reading-frame (PMID: 25491247). This variant disrupts a region of the HGSNAT protein in which other variant(s) (p.Ala489Glu) have been determined to be pathogenic (PMID: 19479962, 19823584, 20583299, 31228227). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Myriad Genetics, Inc.	RCV001810455	SCV002060150	uncertain significance	Mucopolysaccharidosis, MPS-III-C	2021-11-10	criteria provided, single submitter	clinical testing	NM_152419.2(HGSNAT):c.1542+4dupA is an intronic variant classified as a variant of uncertain significance in the context of mucopolysaccharidosis type IIIC. c.1542+4dupA has been observed in cases with relevant disease (PMID: 19479962, 25491247). Functional assessments of this variant are available in the literature (PMID: 25491247). c.1542+4dupA has been observed in population frequency databases (gnomAD: NFE 0.004%). In summary, there is insufficient evidence to classify NM_152419.2(HGSNAT):c.1542+4dupA as pathogenic or benign. Please note: this variant was assessed in the context of healthy population screening.
NIHR Bioresource Rare Diseases, University of Cambridge	RCV000505003	SCV000599071	likely pathogenic	Retinal dystrophy	2015-01-01	no assertion criteria provided	research
Natera, Inc.	RCV001810455	SCV002083322	uncertain significance	Mucopolysaccharidosis, MPS-III-C	2021-04-01	no assertion criteria provided	clinical testing