NM_152419.3(HGSNAT):c.1129-2A>T AND multiple conditions

Clinical significance:Likely pathogenic (Last evaluated: Aug 3, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001069675.2

Allele description [Variation Report for NM_152419.3(HGSNAT):c.1129-2A>T]

NM_152419.3(HGSNAT):c.1129-2A>T

Gene:
HGSNAT:heparan-alpha-glucosaminide N-acetyltransferase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
8p11.21
Genomic location:
Preferred name:
NM_152419.3(HGSNAT):c.1129-2A>T
HGVS:
  • NC_000008.11:g.43191472A>T
  • NG_009552.1:g.56024A>T
  • NM_001363227.2:c.1129-2A>T
  • NM_001363228.2:c.937-2A>T
  • NM_001363229.2:c.265-2A>T
  • NM_152419.3:c.1129-2A>TMANE SELECT
  • NC_000008.10:g.43046615A>T
  • NM_152419.2:c.1129-2A>T
Links:
dbSNP: rs749568919
NCBI 1000 Genomes Browser:
rs749568919
Molecular consequence:
  • NM_001363227.2:c.1129-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001363228.2:c.937-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001363229.2:c.265-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_152419.3:c.1129-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Name:
Mucopolysaccharidosis, MPS-III-C (MPS3C)
Synonyms:
Mucopoly-saccharidosis type 3C; Sanfilippo syndrome C; Acetyl-CoA alpha-glucosaminide n-acetyltransferase deficiency; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0009657; MedGen: C0086649; Orphanet: 581; Orphanet: 79271; OMIM: 252930
Name:
Retinitis pigmentosa 73 (RP73)
Identifiers:
MONDO: MONDO:0014687; MedGen: C4225287; Orphanet: 791; OMIM: 616544

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001234861Invitaecriteria provided, single submitter
Likely pathogenic
(Aug 3, 2020)
germlineclinical testing

PubMed (4)
[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

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]
PMID:
16199547
PMCID:
PMC1735933

Mutations in TMEM76* cause mucopolysaccharidosis IIIC (Sanfilippo C syndrome).

Hrebícek M, Mrázová L, Seyrantepe V, Durand S, Roslin NM, Nosková L, Hartmannová H, Ivánek R, Cízkova A, Poupetová H, Sikora J, Urinovská J, Stranecký V, Zeman J, Lepage P, Roquis D, Verner A, Ausseil J, Beesley CE, Maire I, Poorthuis BJ, van de Kamp J, et al.

Am J Hum Genet. 2006 Nov;79(5):807-19. Epub 2006 Sep 8.

PubMed [citation]
PMID:
17033958
PMCID:
PMC1698556
See all PubMed Citations (4)

Details of each submission

From Invitae, SCV001234861.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

This sequence change affects an acceptor splice site in intron 11 of the HGSNAT gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is present in population databases (rs749568919, ExAC 0.001%). This variant has not been reported in the literature in individuals with HGSNAT-related conditions. ClinVar contains an entry for this variant (Variation ID: 554389). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in HGSNAT are known to be pathogenic (PMID: 17033958, 19479962). 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.

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

Last Updated: Nov 27, 2021

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