NM_000199.5(SGSH):c.817G>A (p.Asp273Asn) AND not specified

Clinical significance:Uncertain significance (Last evaluated: Jan 15, 2021)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000781846.3

Allele description [Variation Report for NM_000199.5(SGSH):c.817G>A (p.Asp273Asn)]

NM_000199.5(SGSH):c.817G>A (p.Asp273Asn)

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.817G>A (p.Asp273Asn)
HGVS:
  • NC_000017.11:g.80212203C>T
  • NG_008229.1:g.13198G>A
  • NM_000199.5:c.817G>AMANE SELECT
  • NM_001352921.2:c.817G>A
  • NM_001352922.2:c.817G>A
  • NP_000190.1:p.Asp273Asn
  • NP_001339850.1:p.Asp273Asn
  • NP_001339851.1:p.Asp273Asn
  • NC_000017.10:g.78186002C>T
  • NM_000199.3:c.817G>A
  • NR_148201.2:n.731G>A
Protein change:
D273N
Links:
dbSNP: rs1046551417
NCBI 1000 Genomes Browser:
rs1046551417
Molecular consequence:
  • NM_000199.5:c.817G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001352921.2:c.817G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001352922.2:c.817G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NR_148201.2:n.731G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000920208Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Uncertain significance
(Jan 15, 2021)
germlineclinical testing

PubMed (7)
[See all records that cite these PMIDs]

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Transport, enzymatic activity, and stability of mutant sulfamidase (SGSH) identified in patients with mucopolysaccharidosis type III A.

Muschol N, Storch S, Ballhausen D, Beesley C, Westermann JC, Gal A, Ullrich K, Hopwood JJ, Winchester B, Braulke T.

Hum Mutat. 2004 Jun;23(6):559-66.

PubMed [citation]
PMID:
15146460

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
See all PubMed Citations (7)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000920208.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (7)

Description

Variant summary: SGSH c.817G>A (p.Asp273Asn) results in a conservative amino acid change located in the Sulfatase, N-terminal domain (IPR000917) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8e-06 in 250174 control chromosomes (gnomAD) and been reported in the literature in individuals affected with Mucopolysaccharidosis Type IIIA (Sanfilippo Syndrome A) (Beesley_2000, Truxal_2016). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. However, based on the atomic structure of SGSH, Sidhu et. al. report that this variant may disrupts Ca2+ binding (Sidhu_2013). Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as pathogenic and one laboratory classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jun 14, 2021

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