NM_000512.5(GALNS):c.1365-2A>G AND Mucopolysaccharidosis, MPS-IV-A

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Jan 15, 2025
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:: RCV003313762.4

Allele description [Variation Report for NM_000512.5(GALNS):c.1365-2A>G]

NM_000512.5(GALNS):c.1365-2A>G

Genes:

LOC126862447:CDK7 strongly-dependent group 2 enhancer GRCh37_chr16:88884193-88885392 [Gene]
GALNS:galactosamine (N-acetyl)-6-sulfatase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

16q24.3

Genomic location:

Preferred name:

NM_000512.5(GALNS):c.1365-2A>G

HGVS:

NC_000016.10:g.88818126T>C
NG_008667.1:g.43841A>G
NG_086945.1:g.442T>C
NM_000512.5:c.1365-2A>GMANE SELECT
NM_001323543.2:c.810-2A>G
NM_001323544.2:c.1383-2A>G
NC_000016.9:g.88884534T>C

Molecular consequence:

NM_000512.5:c.1365-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001323543.2:c.810-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001323544.2:c.1383-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Name:: Mucopolysaccharidosis, MPS-IV-A (MPS4A)
Synonyms:: MORQUIO SYNDROME A; GALACTOSAMINE-6-SULFATASE DEFICIENCY; GALNS DEFICIENCY; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009659; MedGen: C0086651; Orphanet: 309297; Orphanet: 582; OMIM: 253000

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004012876	Molecular Biology Laboratory, Department of Zoology, Quaid-i-azam University	no assertion criteria provided	association not found	inherited	research
SCV004487079	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 15, 2025)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 16199547, 12442278, 25545067, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004012876

Molecular Biology Laboratory, Department of Zoology, Quaid-i-azam University

no assertion criteria provided

association not found

inherited

research

SCV004487079

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 15, 2025)

germline

clinical testing

PubMed (4)
[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	inherited	yes	not provided	not provided	not provided	not provided	not provided	research
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]

PMID:: 16199547
PMCID:: PMC1735933

Molecular analysis of Turkish mucopolysaccharidosis IVA (Morquio A) patients: identification of novel mutations in the N-acetylgalactosamine-6-sulfate sulfatase (GALNS) gene.

Terzioglu M, Tokatli A, Coskun T, Emre S.

Hum Mutat. 2002 Dec;20(6):477-8.

PubMed [citation]

PMID:: 12442278

See all PubMed Citations (4)

Details of each submission

From Molecular Biology Laboratory, Department of Zoology, Quaid-i-azam University, SCV004012876.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	research	not provided

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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004487079.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change affects an acceptor splice site in intron 12 of the GALNS gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in GALNS are known to be pathogenic (PMID: 12442278). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with mucopolysaccharidosis type IVA (PMID: 25545067). ClinVar contains an entry for this variant (Variation ID: 2572062). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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: Mar 11, 2025

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