NM_152419.3(HGSNAT):c.1401del (p.Tyr468fs) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 17, 2023
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:: RCV003813212.2

Allele description [Variation Report for NM_152419.3(HGSNAT):c.1401del (p.Tyr468fs)]

NM_152419.3(HGSNAT):c.1401del (p.Tyr468fs)

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.1401del (p.Tyr468fs)

HGVS:

NC_000008.11:g.43193780del
NG_009552.1:g.58332del
NM_001363227.2:c.1401del
NM_001363228.2:c.1209del
NM_001363229.2:c.537del
NM_152419.3:c.1401delMANE SELECT
NP_001350156.1:p.Tyr468fs
NP_001350157.1:p.Tyr404fs
NP_001350158.1:p.Tyr180fs
NP_689632.2:p.Tyr468fs
NC_000008.10:g.43048922del
NC_000008.10:g.43048923del

Protein change:

Y180fs

Molecular consequence:

NM_001363227.2:c.1401del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001363228.2:c.1209del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001363229.2:c.537del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_152419.3:c.1401del - 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

Name:: Retinitis pigmentosa 73 (RP73)
Identifiers:: MONDO: MONDO:0014687; MedGen: C4225287; Orphanet: 791; OMIM: 616544

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004609594	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 17, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 17033958, 19479962, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004609594

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 17, 2023)

germline

clinical testing

PubMed (3)
[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

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

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004609594.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change creates a premature translational stop signal (p.Tyr468Metfs*14) in the HGSNAT gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in HGSNAT are known to be pathogenic (PMID: 17033958, 19479962). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with HGSNAT-related conditions. For these reasons, this variant has been classified as Pathogenic.

#	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: Sep 29, 2024

ClinVar

Relating variation to medicine