NM_152419.3(HGSNAT):c.1411G>C (p.Glu471Gln) AND multiple conditions

This record was updated by the submitter. Please see the current version.

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Nov 26, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV001340284.3

Allele description

NM_152419.3(HGSNAT):c.1411G>C (p.Glu471Gln)

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.1411G>C (p.Glu471Gln)

HGVS:

NC_000008.11:g.43193790G>C
NG_009552.1:g.58342G>C
NM_001363227.2:c.1411G>C
NM_001363228.2:c.1219G>C
NM_001363229.2:c.547G>C
NM_152419.3:c.1411G>CMANE SELECT
NP_001350156.1:p.Glu471Gln
NP_001350157.1:p.Glu407Gln
NP_001350158.1:p.Glu183Gln
NP_689632.2:p.Glu471Gln
NC_000008.10:g.43048933G>C

Protein change:

E183Q

Links:

dbSNP: rs753355844

NCBI 1000 Genomes Browser:

rs753355844

Molecular consequence:

NM_001363227.2:c.1411G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001363228.2:c.1219G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001363229.2:c.547G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_152419.3:c.1411G>C - missense variant - [Sequence Ontology: SO:0001583]

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001534085	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Nov 26, 2022)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 17033958, 18024218, 19479962, 20583299, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001534085

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Nov 26, 2022)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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

Clinical and genetic spectrum of Sanfilippo type C (MPS IIIC) disease in The Netherlands.

Ruijter GJ, Valstar MJ, van de Kamp JM, van der Helm RM, Durand S, van Diggelen OP, Wevers RA, Poorthuis BJ, Pshezhetsky AV, Wijburg FA.

Mol Genet Metab. 2008 Feb;93(2):104-11. Epub 2007 Nov 19.

PubMed [citation]

PMID:: 18024218

See all PubMed Citations (5)

Details of each submission

From Invitae, SCV001534085.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change replaces glutamic acid, which is acidic and polar, with glutamine, which is neutral and polar, at codon 471 of the HGSNAT protein (p.Glu471Gln). 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. This variant disrupts the p.Glu471 amino acid residue in HGSNAT. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 17033958, 18024218, 19479962, 20583299). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 1037171). This variant has not been reported in the literature in individuals affected with HGSNAT-related conditions. This variant is not present in population databases (gnomAD no frequency).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Mar 5, 2024

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