NM_000199.5(SGSH):c.736A>G (p.Met246Val) AND Mucopolysaccharidosis, MPS-III-A

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 5, 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:: RCV002632645.2

Allele description [Variation Report for NM_000199.5(SGSH):c.736A>G (p.Met246Val)]

NM_000199.5(SGSH):c.736A>G (p.Met246Val)

Gene:

SGSH:N-sulfoglucosamine sulfohydrolase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17q25.3

Genomic location:

Preferred name:

NM_000199.5(SGSH):c.736A>G (p.Met246Val)

HGVS:

NC_000017.11:g.80213813T>C
NG_008229.2:g.11520A>G
NM_000199.5:c.736A>GMANE SELECT
NM_001352921.3:c.736A>G
NM_001352922.2:c.736A>G
NP_000190.1:p.Met246Val
NP_001339850.1:p.Met246Val
NP_001339851.1:p.Met246Val
NC_000017.10:g.78187612T>C
NG_008229.1:g.11588A>G
NR_148201.2:n.650A>G

Protein change:

M246V

Molecular consequence:

NM_000199.5:c.736A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001352921.3:c.736A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001352922.2:c.736A>G - missense variant - [Sequence Ontology: SO:0001583]
NR_148201.2:n.650A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Mucopolysaccharidosis, MPS-III-A (MPS3A)
Synonyms:: SULFAMIDASE DEFICIENCY; Mucopoly-saccharidosis type 3A; Sanfilippo syndrome A; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009655; MedGen: C0086647; Orphanet: 581; Orphanet: 79269; OMIM: 252900

Recent activity

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chloride channel CLIC-like protein 1 isoform 2 precursor [Homo sapiens]
chloride channel CLIC-like protein 1 isoform 2 precursor [Homo sapiens]
gi|13194195|ref|NP_055942.1|

Protein
SERINC1 serine incorporator 1 [Homo sapiens]
SERINC1 serine incorporator 1 [Homo sapiens]
Gene ID:57515

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003504290	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 5, 2021)	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

SCV003504290

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 5, 2021)

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, SCV003504290.1

#	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 methionine with valine at codon 246 of the SGSH protein (p.Met246Val). The methionine residue is moderately conserved and there is a small physicochemical difference between methionine and valine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with SGSH-related conditions. 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 SGSH 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: Sep 29, 2024

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