NM_152419.3(HGSNAT):c.65del (p.Leu22fs) AND multiple conditions

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Jan 8, 2025
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:: RCV005051631.3

Allele description [Variation Report for NM_152419.3(HGSNAT):c.65del (p.Leu22fs)]

NM_152419.3(HGSNAT):c.65del (p.Leu22fs)

Genes:

LOC130000316:ATAC-STARR-seq lymphoblastoid silent region 19164 [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.65del (p.Leu22fs)

HGVS:

NC_000008.11:g.43140561del
NG_009552.1:g.5113del
NG_179762.1:g.398del
NM_001363227.2:c.65del
NM_001363228.2:c.65del
NM_001363229.2:c.-769del
NM_152419.3:c.65delMANE SELECT
NP_001350156.1:p.Leu22fs
NP_001350157.1:p.Leu22fs
NP_689632.2:p.Leu22fs
NC_000008.10:g.42995704del

Protein change:

L22fs

Molecular consequence:

NM_001363229.2:c.-769del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001363227.2:c.65del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001363228.2:c.65del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_152419.3:c.65del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Mucopolysaccharidosis, MPS-III-C (MPS3C)
Synonyms:: SANFILIPPO SYNDROME C; MPS III C; MUCOPOLYSACCHARIDOSIS, TYPE IIIC; 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
SCV005675473	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Apr 23, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV005864526	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 8, 2025)	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

SCV005675473

Fulgent Genetics, Fulgent Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Apr 23, 2024)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV005864526

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 8, 2025)

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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

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 Fulgent Genetics, Fulgent Genetics, SCV005675473.1

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

#	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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV005864526.2

#	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.Leu22Argfs*20) 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: Feb 23, 2026

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