NM_000199.5(SGSH):c.1412G>A (p.Trp471Ter) AND Mucopolysaccharidosis, MPS-III-A

Clinical significance:Pathogenic (Last evaluated: Sep 16, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001389672.1

Allele description [Variation Report for NM_000199.5(SGSH):c.1412G>A (p.Trp471Ter)]

NM_000199.5(SGSH):c.1412G>A (p.Trp471Ter)

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.1412G>A (p.Trp471Ter)
HGVS:
  • NC_000017.11:g.80210549C>T
  • NG_008229.1:g.14852G>A
  • NG_032778.1:g.45558C>T
  • NM_000199.5:c.1412G>AMANE SELECT
  • NM_001352921.3:c.*499G>A
  • NM_001352922.2:c.*462G>A
  • NP_000190.1:p.Trp471Ter
  • LRG_1330:g.45558C>T
  • NC_000017.10:g.78184348C>T
  • NR_148201.2:n.1326G>A
Protein change:
W471*
Molecular consequence:
  • NM_001352921.3:c.*499G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_001352922.2:c.*462G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NR_148201.2:n.1326G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NM_000199.5:c.1412G>A - nonsense - [Sequence Ontology: SO:0001587]

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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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001591121Invitaecriteria provided, single submitter
Pathogenic
(Sep 16, 2020)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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

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):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV001591121.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This sequence change results in a premature translational stop signal in the SGSH gene (p.Trp471*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 32 amino acids of the SGSH protein. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with SGSH-related conditions. This variant disrupts the C-terminus of the SGSH protein. Other variant(s) that disrupt this region (p.Trp479*) have been determined to be pathogenic (PMID: 21204211). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: May 14, 2021

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