Submissions for variant NM_152419.3(HGSNAT):c.493C>T (p.Pro165Ser)

gnomAD frequency: 0.00016  dbSNP: rs371273730

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV001164228	SCV001326341	uncertain significance	Mucopolysaccharidosis, MPS-III-C	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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001246133	SCV001419473	uncertain significance	Mucopolysaccharidosis, MPS-III-C; Retinitis pigmentosa 73	2022-09-19	criteria provided, single submitter	clinical testing	This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 165 of the HGSNAT protein (p.Pro165Ser). This variant is present in population databases (rs371273730, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with HGSNAT-related conditions. ClinVar contains an entry for this variant (Variation ID: 911654). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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.
GeneDx	RCV004590110	SCV005078486	uncertain significance	not provided	2024-07-11	criteria provided, single submitter	clinical testing	Identified in the heterozygous state in an individual with extensive dermal melanocytosis, generalized hypertrichosis, and chronic itch without other features of MPS IIIC; a second variant was not identified (PMID: 38136122); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 38136122)
Natera, Inc.	RCV001164228	SCV002083283	uncertain significance	Mucopolysaccharidosis, MPS-III-C	2020-04-14	no assertion criteria provided	clinical testing
Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg	RCV004813819	SCV005072562	uncertain significance	Retinal dystrophy	2022-01-01	no assertion criteria provided	clinical testing