ClinVar Miner

Submissions for variant NM_152419.3(HGSNAT):c.947G>A (p.Trp316Ter)

dbSNP: rs1554533211
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000668961 SCV000793646 likely pathogenic Mucopolysaccharidosis, MPS-III-C 2017-08-22 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001264578 SCV001442801 likely pathogenic Sanfilippo syndrome 2020-10-14 criteria provided, single submitter clinical testing Variant summary: HGSNAT c.947G>A (p.Trp316X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 239666 control chromosomes (gnomAD). c.947G>A has been reported in the literature in individuals affected with Mucopolysaccharidosis Type IIIC (Sanfilippo Syndrome C) (e.g. Hrebicek_2006, Ghosh_2017). These data indicate that the variant may be associated with disease. Experimental evidence indicated deficient HGSNAT activity in leukocytes of a compound heterozygous patient with the variant (Ghosh_2017). A ClinVar submitter (evaluation after 2014) cites the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV001855511 SCV002232959 pathogenic Mucopolysaccharidosis, MPS-III-C; Retinitis pigmentosa 73 2023-09-29 criteria provided, single submitter clinical testing This premature translational stop signal has been observed in individual(s) with mucopolysaccharidosis IIIC (PMID: 17033958, 28468868). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Trp316*) in the HGSNAT gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in HGSNAT are known to be pathogenic (PMID: 17033958, 19479962). ClinVar contains an entry for this variant (Variation ID: 553494). For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics RCV001855511 SCV005675488 pathogenic Mucopolysaccharidosis, MPS-III-C; Retinitis pigmentosa 73 2024-03-20 criteria provided, single submitter clinical testing

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