NM_000199.5(SGSH):c.268G>C (p.Gly90Arg) AND Mucopolysaccharidosis, MPS-III-A

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jan 29, 2020
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:: RCV001377322.7

Allele description [Variation Report for NM_000199.5(SGSH):c.268G>C (p.Gly90Arg)]

NM_000199.5(SGSH):c.268G>C (p.Gly90Arg)

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.268G>C (p.Gly90Arg)

HGVS:

NC_000017.11:g.80215120C>G
NG_008229.1:g.10281G>C
NM_000199.5:c.268G>CMANE SELECT
NM_001352921.3:c.268G>C
NM_001352922.2:c.268G>C
NP_000190.1:p.Gly90Arg
NP_001339850.1:p.Gly90Arg
NP_001339851.1:p.Gly90Arg
NC_000017.10:g.78188919C>G

Protein change:

G90R

Links:

dbSNP: rs774010006

NCBI 1000 Genomes Browser:

rs774010006

Molecular consequence:

NM_000199.5:c.268G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001352921.3:c.268G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001352922.2:c.268G>C - missense variant - [Sequence Ontology: SO:0001583]

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
SCV001574628	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Jan 29, 2020)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 21204211, 21455105, 24875751, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001574628

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Jan 29, 2020)

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

Incidence and natural history of mucopolysaccharidosis type III in France and comparison with United Kingdom and Greece.

Héron B, Mikaeloff Y, Froissart R, Caridade G, Maire I, Caillaud C, Levade T, Chabrol B, Feillet F, Ogier H, Valayannopoulos V, Michelakakis H, Zafeiriou D, Lavery L, Wraith E, Danos O, Heard JM, Tardieu M.

Am J Med Genet A. 2011 Jan;155A(1):58-68. doi: 10.1002/ajmg.a.33779.

PubMed [citation]

PMID:: 21204211

Two-year follow-up of Sanfilippo Disease patients treated with a genistein-rich isoflavone extract: assessment of effects on cognitive functions and general status of patients.

Piotrowska E, Jakobkiewicz-Banecka J, Maryniak A, Tylki-Szymanska A, Puk E, Liberek A, Wegrzyn A, Czartoryska B, Slominska-Wojewodzka M, Wegrzyn G.

Med Sci Monit. 2011 Apr;17(4):CR196-202.

PubMed [citation]

PMID:: 21455105
PMCID:: PMC3539518

See all PubMed Citations (4)

Details of each submission

From Invitae, SCV001574628.5

#	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 with arginine at codon 90 of the SGSH protein (p.Gly90Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. 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. A different variant (c.268G>A) giving rise to the same protein effect observed here (p.Gly90Arg) has been determined to be pathogenic (PMID: 21204211, 21455105, 24875751). This suggests that this variant is also likely to be causative of disease. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with SGSH-related conditions. This variant is not present in population databases (ExAC no frequency).

#	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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