NM_152419.3(HGSNAT):c.1330C>T (p.Arg444Cys) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 23, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV002554715.2

Allele description [Variation Report for NM_152419.3(HGSNAT):c.1330C>T (p.Arg444Cys)]

NM_152419.3(HGSNAT):c.1330C>T (p.Arg444Cys)

Gene:

HGSNAT:heparan-alpha-glucosaminide N-acetyltransferase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

8p11.21

Genomic location:

Preferred name:

NM_152419.3(HGSNAT):c.1330C>T (p.Arg444Cys)

HGVS:

NC_000008.11:g.43192383C>T
NG_009552.1:g.56935C>T
NM_001363227.2:c.1330C>T
NM_001363228.2:c.1138C>T
NM_001363229.2:c.466C>T
NM_152419.3:c.1330C>TMANE SELECT
NP_001350156.1:p.Arg444Cys
NP_001350157.1:p.Arg380Cys
NP_001350158.1:p.Arg156Cys
NP_689632.2:p.Arg444Cys
NC_000008.10:g.43047526C>T
NC_000008.10:g.43047526C>T
NM_152419.2:c.1330C>T
p.R444C

Protein change:

R156C

Links:

dbSNP: rs763301637

NCBI 1000 Genomes Browser:

rs763301637

Molecular consequence:

NM_001363227.2:c.1330C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001363228.2:c.1138C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001363229.2:c.466C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_152419.3:c.1330C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Mucopolysaccharidosis, MPS-III-C (MPS3C)
Synonyms:: SANFILIPPO SYNDROME C; Mucopoly-saccharidosis type 3C; Acetyl-CoA alpha-glucosaminide n-acetyltransferase deficiency; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009657; MedGen: C0086649; Orphanet: 581; Orphanet: 79271; OMIM: 252930

Name:: Retinitis pigmentosa 73 (RP73)
Identifiers:: MONDO: MONDO:0014687; MedGen: C4225287; Orphanet: 791; OMIM: 616544

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003293969	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 23, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003293969

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 23, 2022)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group, Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003293969.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 444 of the HGSNAT protein (p.Arg444Cys). This variant is present in population databases (no rsID available, gnomAD 0.003%). This missense change has been observed in individual(s) with retinitis pigmentosa (Invitae). ClinVar contains an entry for this variant (Variation ID: 866424). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt HGSNAT protein function. 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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jan 13, 2025

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