NM_000199.5(SGSH):c.703G>C (p.Asp235His) AND Mucopolysaccharidosis, MPS-III-A

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jul 7, 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:: RCV003613729.1

Allele description [Variation Report for NM_000199.5(SGSH):c.703G>C (p.Asp235His)]

NM_000199.5(SGSH):c.703G>C (p.Asp235His)

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.703G>C (p.Asp235His)

HGVS:

NC_000017.11:g.80213846C>G
NG_008229.1:g.11555G>C
NG_008229.2:g.11487G>C
NM_000199.5:c.703G>CMANE SELECT
NM_001352921.3:c.703G>C
NM_001352922.2:c.703G>C
NP_000190.1:p.Asp235His
NP_001339850.1:p.Asp235His
NP_001339851.1:p.Asp235His
NC_000017.10:g.78187645C>G
NR_148201.2:n.617G>C

Protein change:

D235H

Molecular consequence:

NM_000199.5:c.703G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001352921.3:c.703G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001352922.2:c.703G>C - missense variant - [Sequence Ontology: SO:0001583]
NR_148201.2:n.617G>C - 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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004491020	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Jul 7, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 11182930, 12000360, 19099774, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004491020

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Jul 7, 2023)

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

Mutational analysis of Sanfilippo syndrome type A (MPS IIIA): identification of 13 novel mutations.

Beesley CE, Young EP, Vellodi A, Winchester BG.

J Med Genet. 2000 Sep;37(9):704-7. No abstract available.

PubMed [citation]

PMID:: 11182930
PMCID:: PMC1734705

Identification and characterization of mutations underlying Sanfilippo syndrome type A (mucopolysaccharidosis type IIIA).

Lee-Chen GJ, Lin SP, Ko MH, Chuang CK, Chen CP, Lee HH, Cheng SC, Shen CH, Tseng KL, Li CL.

Clin Genet. 2002 Mar;61(3):192-7.

PubMed [citation]

PMID:: 12000360

See all PubMed Citations (4)

Details of each submission

From Invitae, SCV004491020.1

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

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Asp235 amino acid residue in SGSH. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 11182930, 12000360, 19099774; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. This variant has not been reported in the literature in individuals affected with SGSH-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with histidine, which is basic and polar, at codon 235 of the SGSH protein (p.Asp235His).

#	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: Feb 28, 2024

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