NM_152419.3(HGSNAT):c.1271dup (p.Ile425fs) AND Sanfilippo syndrome

Clinical significance:Pathogenic (Last evaluated: Mar 20, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001175525.1

Allele description [Variation Report for NM_152419.3(HGSNAT):c.1271dup (p.Ile425fs)]

NM_152419.3(HGSNAT):c.1271dup (p.Ile425fs)

Gene:
HGSNAT:heparan-alpha-glucosaminide N-acetyltransferase [Gene - OMIM - HGNC]
Variant type:
Duplication
Cytogenetic location:
8p11.21
Genomic location:
Preferred name:
NM_152419.3(HGSNAT):c.1271dup (p.Ile425fs)
HGVS:
  • NC_000008.11:g.43192324dup
  • NG_009552.1:g.56876dup
  • NM_001363227.2:c.1271dup
  • NM_001363228.2:c.1079dup
  • NM_001363229.2:c.407dup
  • NM_152419.3:c.1271dupMANE SELECT
  • NP_001350156.1:p.Ile425fs
  • NP_001350157.1:p.Ile361fs
  • NP_001350158.1:p.Ile137fs
  • NP_689632.2:p.Ile425fs
  • NC_000008.10:g.43047462_43047463insG
  • NC_000008.10:g.43047467dup
  • NM_152419.2:c.1271dupG
Protein change:
I137fs
Links:
dbSNP: rs1804565177
NCBI 1000 Genomes Browser:
rs1804565177
Molecular consequence:
  • NM_001363227.2:c.1271dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001363228.2:c.1079dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001363229.2:c.407dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_152419.3:c.1271dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:
Sanfilippo syndrome
Synonyms:
Mucopolysaccharidosis type III; Mucopoly-saccharidosis type 3; Mucopolysaccharidosis type 3; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0018937; MedGen: C0026706

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001339133Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Pathogenic
(Mar 20, 2020)
germlineclinical testing

PubMed (2)
[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

Sanfilippo syndrome type C: mutation spectrum in the heparan sulfate acetyl-CoA: alpha-glucosaminide N-acetyltransferase (HGSNAT) gene.

Feldhammer M, Durand S, Mrázová L, Boucher RM, Laframboise R, Steinfeld R, Wraith JE, Michelakakis H, van Diggelen OP, Hrebícek M, Kmoch S, Pshezhetsky AV.

Hum Mutat. 2009 Jun;30(6):918-25. doi: 10.1002/humu.20986. Review.

PubMed [citation]
PMID:
19479962

Molecular characterization of a large group of Mucopolysaccharidosis type IIIC patients reveals the evolutionary history of the disease.

Martins C, de Medeiros PFV, Leistner-Segal S, Dridi L, Elcioglu N, Wood J, Behnam M, Noyan B, Lacerda L, Geraghty MT, Labuda D, Giugliani R, Pshezhetsky AV.

Hum Mutat. 2019 Aug;40(8):1084-1100. doi: 10.1002/humu.23752. Epub 2019 Jun 22.

PubMed [citation]
PMID:
31228227

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001339133.1

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

Description

Variant summary: HGSNAT c.1271dupG (p.Ile425HisfsX45) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant was absent in 240376 control chromosomes (gnomAD). c.1271dupG has been reported in the literature in individuals affected with Mucopolysaccharidosis Type IIIC (Sanfilippo Syndrome C) (Feldhammer_2009, Martins_2019). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic.

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

Last Updated: Nov 27, 2021

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