NM_152419.3(HGSNAT):c.1267G>T (p.Gly423Trp) AND Sanfilippo syndrome

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Aug 30, 2023
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:: RCV003330719.2

Allele description [Variation Report for NM_152419.3(HGSNAT):c.1267G>T (p.Gly423Trp)]

NM_152419.3(HGSNAT):c.1267G>T (p.Gly423Trp)

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.1267G>T (p.Gly423Trp)

HGVS:

NC_000008.11:g.43192320G>T
NG_009552.1:g.56872G>T
NM_001363227.2:c.1267G>T
NM_001363228.2:c.1075G>T
NM_001363229.2:c.403G>T
NM_152419.3:c.1267G>TMANE SELECT
NP_001350156.1:p.Gly423Trp
NP_001350157.1:p.Gly359Trp
NP_001350158.1:p.Gly135Trp
NP_689632.2:p.Gly423Trp
NC_000008.10:g.43047463G>T
NM_152419.2:c.1267G>T
p.G423W

Protein change:

G135W

Links:

dbSNP: rs1064795522

NCBI 1000 Genomes Browser:

rs1064795522

Molecular consequence:

NM_001363227.2:c.1267G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001363228.2:c.1075G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001363229.2:c.403G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_152419.3:c.1267G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Sanfilippo syndrome
Synonyms:: Mucopolysaccharidosis type III; Mucopoly-saccharidosis type 3; Mucopolysaccharidosis type 3; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0018937; MedGen: C0026706

Recent activity

Clear Turn Off Turn On

carboxyl- protease [Coprothermobacter proteolyticus DSM 5265]
carboxyl- protease [Coprothermobacter proteolyticus DSM 5265]
gi|206738279|gb|ACI17357.1||gnl|PRJ 29|COPRO5265_0551

Protein

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000699949	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Likely pathogenic (Aug 30, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 31228227, 35848209 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000699949

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Likely pathogenic
(Aug 30, 2023)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

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

Molecular characterization of a large group of Mucopolysaccharidosis type IIIC patients reveals the evolutionary history of the disease.

Martins C, de Medeiros PFV, Leistner-Segal S, Dridi L, Elcioglu N, Wood J, Behnam M, Noyan B, Lacerda L, Geraghty MT, Labuda D, Giugliani R, Pshezhetsky AV.

Hum Mutat. 2019 Aug;40(8):1084-1100. doi: 10.1002/humu.23752. Epub 2019 Jun 22.

PubMed [citation]

PMID:: 31228227

Adults with lysosomal storage diseases in the undiagnosed diseases network.

Xiao C, Koziura M, Cope H, Spillman R, Tan K, Hisama FM, Tifft CJ, Toro C.

Mol Genet Genomic Med. 2022 Sep;10(9):e2013. doi: 10.1002/mgg3.2013. Epub 2022 Jul 18.

PubMed [citation]

PMID:: 35848209
PMCID:: PMC9482386

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000699949.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

Variant summary: HGSNAT c.1267G>T (p.Gly423Trp) results in a non-conservative amino acid change in the encoded protein sequence. Four of four in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 241552 control chromosomes. c.1267G>T has been reported in the literature in individuals affected with Mucopolysaccharidosis Type IIIC (Sanfilippo Syndrome C) (Martins_2019, Xiao_2022). At least one publication reports experimental evidence evaluating an impact on protein function demonstrates that this variant shows negligible enzyme activity (Martins_2010) . The following publications have been ascertained in the context of this evaluation (PMID: 31228227, 35848209). Four submitters have cited clinical-significance assessments for this variant to ClinVar after 2014 and classified as pathogenic/likely pathogenic (n=3) and VUS (n=1). Based on the evidence outlined above, the variant was classified as likely pathogenic.

#	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: Sep 29, 2024

ClinVar

Relating variation to medicine