NM_152419.3(HGSNAT):c.743G>C (p.Gly248Ala) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 6, 2021
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:: RCV001879808.3

Allele description [Variation Report for NM_152419.3(HGSNAT):c.743G>C (p.Gly248Ala)]

NM_152419.3(HGSNAT):c.743G>C (p.Gly248Ala)

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.743G>C (p.Gly248Ala)

HGVS:

NC_000008.11:g.43170694G>C
NG_009552.1:g.35246G>C
NM_001363227.2:c.743G>C
NM_001363228.2:c.743G>C
NM_001363229.2:c.-91G>C
NM_152419.3:c.743G>CMANE SELECT
NP_001350156.1:p.Gly248Ala
NP_001350157.1:p.Gly248Ala
NP_689632.2:p.Gly248Ala
NC_000008.10:g.43025837G>C
NC_000008.10:g.43025837G>C
NM_152419.2:c.743G>C

Protein change:

G248A

Links:

dbSNP: rs1324238938

NCBI 1000 Genomes Browser:

rs1324238938

Molecular consequence:

NM_001363229.2:c.-91G>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001363227.2:c.743G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001363228.2:c.743G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_152419.3:c.743G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Mucopolysaccharidosis, MPS-III-C (MPS3C)
Synonyms:: Mucopoly-saccharidosis type 3C; Sanfilippo syndrome C; 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
SCV002298135	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 6, 2021)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 32770643, 17576681, 9536098, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002298135

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 6, 2021)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

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

A genetic and clinical study of individuals with nonsyndromic retinopathy consequent upon sequence variants in HGSNAT, the gene associated with Sanfilippo C mucopolysaccharidosis.

Schiff ER, Daich Varela M, Robson AG, Pierpoint K, Ba-Abbad R, Nutan S, Zein WM, Ullah E, Huryn LA, Tuupanen S, Mahroo OA, Michaelides M, Burke D, Harvey K, Arno G, Hufnagel RB, Webster AR.

Am J Med Genet C Semin Med Genet. 2020 Sep;184(3):631-643. doi: 10.1002/ajmg.c.31822. Epub 2020 Aug 7.

PubMed [citation]

PMID:: 32770643
PMCID:: PMC8125330

Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization.

Buratti E, Chivers M, Královicová J, Romano M, Baralle M, Krainer AR, Vorechovsky I.

Nucleic Acids Res. 2007;35(13):4250-63. Epub 2007 Jun 18.

PubMed [citation]

PMID:: 17576681
PMCID:: PMC1934990

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002298135.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change replaces glycine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 248 of the HGSNAT protein (p.Gly248Ala). This variant also falls at the last nucleotide of exon 7, which is part of the consensus splice site for this exon. This variant is present in population databases (no rsID available, gnomAD 0.004%). This missense change has been observed in individual(s) with retinitis pigmentosa (PMID: 32770643). ClinVar contains an entry for this variant (Variation ID: 974592). 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"). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). 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.

#	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

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