VCV001048378.4 - ClinVar

NM_000512.5(GALNS):c.[1140-730_1365-1530del;121-2779_567-248del]

Germline

Classification

criteria provided, single submitter. Learn more about how ClinVar calculates review status.

Pathogenic

This classification is based on the single submission received

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

This haplotype includes the following variants

NM_000512.5(GALNS):c.[1140-730_1365-1530del;121-2779_567-248del]

Other names: -
Functional consequence: -
Links: -

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.
GALNS		Gene associated with autosomal recessive phenotype	No evidence available	GRCh38 GRCh37	1166	1480

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-IV-A	Pathogenic (1)	criteria provided, single submitter	Feb 1, 2021	RCV001578480.4

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.	Expand all rows Collapse all rows 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.
Pathogenic (Feb 01, 2021) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Mucopolysaccharidosis, MPS-IV-A	Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova Accession: SCV001547595.4 First in ClinVar: Aug 25, 2021 Last updated: Sep 03, 2023	Publications: PubMed (3) PubMed: 7795586‚ 8651279‚ 34387910 Comment: show Multi-exon deletion (PVS1_very strong); in vivo functional studies supportive of a damaging effect on the gene product (low to null enzymatic activity in homozygotes; PS3_supporting); the prevalence of the variant in affected individuals is significantly increased compared with the prevalence in controls (PS4_supporting); located in a mutational hot spot and/or critical and well-established functional domain without benign variation (PM1_moderate); absent from gnomAD v2.1.1 (PM2_moderate) (less) Observation: 1 Collection method: curation Allele origin: germline Affected status: yes Observation 1 Collection method: curation Allele origin: germline Affected status: yes

Comment:

Multi-exon deletion (PVS1_very strong); in vivo functional studies supportive of a damaging effect on the gene product (low to null enzymatic activity in homozygotes; PS3_supporting); the prevalence of the variant in affected individuals is significantly increased compared with the prevalence in controls (PS4_supporting); located in a mutational hot spot and/or critical and well-established functional domain without benign variation (PM1_moderate); absent from gnomAD v2.1.1 (PM2_moderate)

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Molecular basis of mucopolysaccharidosis IVA (Morquio A syndrome): A review and classification of GALNS gene variants and reporting of 68 novel variants.	Zanetti A	Human mutation	2021	PMID: 34387910
Mucopolysaccharidosis IVA: four new exonic mutations in patients with N-acetylgalactosamine-6-sulfate sulfatase deficiency.	Tomatsu S	American journal of human genetics	1996	PMID: 8651279
Mucopolysaccharidosis IVA: screening and identification of mutations of the N-acetylgalactosamine-6-sulfate sulfatase gene.	Ogawa T	Human molecular genetics	1995	PMID: 7795586

Text-mined citations for this variant ...

Record last updated May 17, 2025

ClinVar Genomic variation as it relates to human health

NM_000512.5(GALNS):c.[1140-730_1365-1530del;121-2779_567-248del]

Variant Details

NM_000512.5(GALNS):c.[1140-730_1365-1530del;121-2779_567-248del]

Genes

Conditions - Germline

Submissions - Germline

Citations for germline classification of this variant

Text-mined citations for this variant ...