VCV000363150.25 - ClinVar

NM_152419.3(HGSNAT):c.1567A>C (p.Lys523Gln)

Germline

Classification

criteria provided, multiple submitters, no conflicts. Learn more about how ClinVar calculates review status.

Benign/Likely benign

6 out of 10 submissions contributed to this classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_152419.3(HGSNAT):c.1567A>C (p.Lys523Gln)

Variation ID: 363150 Accession: VCV000363150.25

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 8p11.21 8: 43197696 (GRCh38) [ NCBI UCSC ] 8: 43052839 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Dec 6, 2016	Apr 13, 2025	Feb 3, 2025

HGVS

Nucleotide	Protein	Molecular consequence
NM_152419.3:c.1567A>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_689632.2:p.Lys523Gln	missense
NM_001363227.2:c.1654A>C	NP_001350156.1:p.Lys552Gln	missense
NM_001363228.2:c.1375A>C	NP_001350157.1:p.Lys459Gln	missense
NM_001363229.2:c.703A>C	NP_001350158.1:p.Lys235Gln	missense
NC_000008.11:g.43197696A>C
NC_000008.10:g.43052839A>C
NG_009552.1:g.62248A>C

... more HGVS ... less HGVS

Protein change

K523Q, K459Q, K235Q, K552Q

Other names

Canonical SPDI

NC_000008.11:43197695:A:C

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

0.04054 (C)

Allele frequency Help The frequency of the allele represented by this VCV record.

The Genome Aggregation Database (gnomAD), exomes 0.00308

The Genome Aggregation Database (gnomAD), exomes 0.00856

Exome Aggregation Consortium (ExAC) 0.01063

The Genome Aggregation Database (gnomAD) 0.03397

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.03550

The Genome Aggregation Database (gnomAD) 0.03631

Trans-Omics for Precision Medicine (TOPMed) 0.03718

1000 Genomes Project 0.04054

1000 Genomes Project 30x 0.04341

Links

ClinGen: CA4736955 dbSNP: rs73569592 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
HGSNAT		Gene associated with autosomal recessive phenotype	Not yet evaluated	GRCh38 GRCh37	1119	1319

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Mucopolysaccharidosis, MPS-III-C Retinitis pigmentosa 73	Benign (1)	criteria provided, single submitter	Feb 3, 2025	RCV000534224.9
Mucopolysaccharidosis, MPS-III-C	Likely benign (2)	criteria provided, single submitter	Apr 27, 2017	RCV000398564.6
not provided	Benign/Likely benign (4)	criteria provided, multiple submitters, no conflicts	Jul 31, 2018	RCV000675865.9
not specified	Benign/Likely benign (3)	criteria provided, multiple submitters, no conflicts	Oct 11, 2021	RCV000592259.8

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Likely benign (Apr 27, 2017) C Contributing to aggregate classification	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019) Method: clinical testing	Mucopolysaccharidosis, MPS-III-C Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000474017.3 First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020	Publications: PubMed (5) PubMed: 19479962‚ 17033958‚ 17397050‚ 19823584‚ 20583299 Comment: This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more) This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. (less)
Benign (Jul 31, 2018) C Contributing to aggregate classification	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV001886752.1 First in ClinVar: Sep 19, 2021 Last updated: Sep 19, 2021	Comment: This variant is associated with the following publications: (PMID: 17033958, 21228398, 19823584, 20981092, 19479962, 20583299)
Likely benign (Oct 11, 2021) C Contributing to aggregate classification	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Women's Health and Genetics/Laboratory Corporation of America, LabCorp Accession: SCV002014885.1 First in ClinVar: Nov 20, 2021 Last updated: Nov 20, 2021
Likely benign (-) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015) Method: not provided	not provided (Autosomal recessive inheritance) Affected status: yes Allele origin: germline	Breakthrough Genomics, Breakthrough Genomics Accession: SCV005223507.1 First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024
Benign (Feb 03, 2025) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Retinitis pigmentosa 73 Mucopolysaccharidosis, MPS-III-C Explanation for multiple conditions: Uncertain. The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases. Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000656047.6 First in ClinVar: Dec 26, 2017 Last updated: Mar 04, 2025
Benign (Jan 05, 2017) C Contributing to aggregate classification	criteria provided, single submitter (EGL Classification Definitions 2015) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Eurofins Ntd Llc (ga) Accession: SCV000700339.3 First in ClinVar: Apr 02, 2018 Last updated: Apr 13, 2025	Publications: PubMed (1) PubMed: 20583299 Other databases http://www.egl-eurofins.com/emvc… http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=HGSNAT Number of individuals with the variant: 2 Zygosity: Single Heterozygote Sex: mixed
Benign (Sep 21, 2017) N Not contributing to aggregate classification	no assertion criteria provided Method: clinical testing	not provided Affected status: unknown Allele origin: unknown	Mayo Clinic Laboratories, Mayo Clinic Accession: SCV000801589.1 First in ClinVar: Aug 05, 2018 Last updated: Aug 05, 2018
Benign (Sep 16, 2020) N Not contributing to aggregate classification	no assertion criteria provided Method: clinical testing	Mucopolysaccharidosis type IIIC Affected status: unknown Allele origin: germline	Natera, Inc. Accession: SCV001460472.1 First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 2021
Likely benign (-) N Not contributing to aggregate classification	no assertion criteria provided Method: clinical testing	not provided Affected status: yes Allele origin: germline	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) Study: VKGL Data-share Consensus Accession: SCV001797490.1 First in ClinVar: Aug 21, 2021 Last updated: Aug 21, 2021
Benign (-) N Not contributing to aggregate classification	no assertion criteria provided Method: clinical testing	not specified Affected status: yes Allele origin: germline	Clinical Genetics, Academic Medical Center Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001923003.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021

Comment:

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Functional analysis of the HGSNAT gene in patients with mucopolysaccharidosis IIIC (Sanfilippo C Syndrome).	Fedele AO	Human mutation	2010	PMID: 20583299
Protein misfolding as an underlying molecular defect in mucopolysaccharidosis III type C.	Feldhammer M	PloS one	2009	PMID: 19823584
Sanfilippo syndrome type C: mutation spectrum in the heparan sulfate acetyl-CoA: alpha-glucosaminide N-acetyltransferase (HGSNAT) gene.	Feldhammer M	Human mutation	2009	PMID: 19479962
Mutational analysis of the HGSNAT gene in Italian patients with mucopolysaccharidosis IIIC (Sanfilippo C syndrome). Mutation in brief #959. Online.	Fedele AO	Human mutation	2007	PMID: 17397050
Mutations in TMEM76* cause mucopolysaccharidosis IIIC (Sanfilippo C syndrome).	Hrebícek M	American journal of human genetics	2006	PMID: 17033958
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=HGSNAT	-	-	-	-

Text-mined citations for rs73569592 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated May 17, 2025

ClinVar Genomic variation as it relates to human health

NM_152419.3(HGSNAT):c.1567A>C (p.Lys523Gln)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs73569592 ...