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NM_152419.3(HGSNAT):c.739del (p.Arg247fs) AND Mucopolysaccharidosis, MPS-III-C

Germline classification:
Pathogenic (2 submissions)
Last evaluated:
Aug 23, 2023
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
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:
RCV000666153.3

Allele description [Variation Report for NM_152419.3(HGSNAT):c.739del (p.Arg247fs)]

NM_152419.3(HGSNAT):c.739del (p.Arg247fs)

Gene:
HGSNAT:heparan-alpha-glucosaminide N-acetyltransferase [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
8p11.21
Genomic location:
Preferred name:
NM_152419.3(HGSNAT):c.739del (p.Arg247fs)
HGVS:
  • NC_000008.11:g.43170690del
  • NG_009552.1:g.35242del
  • NM_001363227.2:c.739del
  • NM_001363228.2:c.739del
  • NM_001363229.2:c.-95del
  • NM_152419.3:c.739delMANE SELECT
  • NP_001350156.1:p.Arg247fs
  • NP_001350157.1:p.Arg247fs
  • NP_689632.2:p.Arg247fs
  • NC_000008.10:g.43025833del
  • NC_000008.11:g.43170690delA
  • NM_152419.2:c.739del
  • NM_152419.2:c.739delA
Protein change:
R247fs
Links:
dbSNP: rs1085307880
NCBI 1000 Genomes Browser:
rs1085307880
Molecular consequence:
  • NM_001363229.2:c.-95del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001363227.2:c.739del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001363228.2:c.739del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_152419.3:c.739del - frameshift variant - [Sequence Ontology: SO:0001589]

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

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000790398Counsyl
criteria provided, single submitter

(Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))		Pathogenic
(Mar 17, 2017) 		unknownclinical testing

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

Citation Link,

SCV004847311Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
criteria provided, single submitter

(ACMG Guidelines, 2015)		Pathogenic
(Aug 23, 2023) 		germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Mutational analysis of the HGSNAT gene in Italian patients with mucopolysaccharidosis IIIC (Sanfilippo C syndrome). Mutation in brief #959. Online.

Fedele AO, Filocamo M, Di Rocco M, Sersale G, Lübke T, di Natale P, Cosma MP, Ballabio A.

Hum Mutat. 2007 May;28(5):523.

PubMed [citation]
PMID:
17397050

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 Counsyl, SCV000790398.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV004847311.1

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

Description

The p.Arg247GlyfsX29 (c.739delA) variant in HGSNAT has been reported in 3 individuals with Mucopolysaccharidosis type IIIC. Two of these individuals were homozygous for this variant, and the third was a compound heterozygote with a pathogenic variant (p.R506X) detected in trans (Fedele 2007 PMID: 17397050, Feldhammer 2009 PMID: 19479962). This variant has also been reported in ClinVar (Variation ID 426971) and was absent from large population studies. This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 247 and leads to a premature termination codon 29 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Loss of function of the HGSNAT gene is an established disease mechanism in autosomal recessive Mucopolysaccharidosis type IIIC (Hrebicek 2006 PMID: 17033958; Feldhammer 2009 PMID: 19479962). In summary, this variant meets criteria to be classified as pathogenic for autosomal recessive Mucopolysaccharidosis type IIIC. ACMG/AMP Criteria applied: PVS1, PM3_Strong, PM2_Supporting.

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

Last Updated: Jun 23, 2024