NM_000512.5(GALNS):c.1417C>T (p.Gln473Ter) AND Mucopolysaccharidosis, MPS-IV-A

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Aug 19, 2022
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:: RCV000000739.11

Allele description [Variation Report for NM_000512.5(GALNS):c.1417C>T (p.Gln473Ter)]

NM_000512.5(GALNS):c.1417C>T (p.Gln473Ter)

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.1417C>T (p.Gln473Ter)

HGVS:

NC_000016.10:g.88818072G>A
NG_008667.1:g.43895C>T
NM_000512.5:c.1417C>TMANE SELECT
NM_001323543.2:c.862C>T
NM_001323544.2:c.1435C>T
NP_000503.1:p.Gln473Ter
NP_001310472.1:p.Gln288Ter
NP_001310473.1:p.Gln479Ter
NC_000016.9:g.88884480G>A

Protein change:

Q288*; GLN473TER

Links:

OMIM: 612222.0006; dbSNP: rs118204439

NCBI 1000 Genomes Browser:

rs118204439

Molecular consequence:

NM_000512.5:c.1417C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001323543.2:c.862C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001323544.2:c.1435C>T - nonsense - [Sequence Ontology: SO:0001587]

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
SCV000020889	OMIM	no assertion criteria provided	Pathogenic (Jan 1, 1995)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV001547962	Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Feb 1, 2021)	germline	curation	PubMed (4) [See all records that cite these PMIDs] 12442278, 7633425, 34387910, 25741868
SCV003443641	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 19, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 7581409, 33752727, 12442278, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000020889

OMIM

no assertion criteria provided

Pathogenic
(Jan 1, 1995)

germline

literature only

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

SCV001547962

Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Feb 1, 2021)

germline

curation

PubMed (4)
[See all records that cite these PMIDs]

SCV003443641

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 19, 2022)

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	germline	yes	not provided	not provided	not provided	not provided	not provided	curation
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mucopolysaccharidosis type IVA: identification of six novel mutations among non-Japanese patients.

Tomatsu S, Fukuda S, Cooper A, Wraith JE, Rezvi GM, Yamagishi A, Yamada N, Kato Z, Isogai K, Sukegawa K, et al.

Hum Mol Genet. 1995 Apr;4(4):741-3. No abstract available.

PubMed [citation]

PMID:: 7633425

Molecular basis of mucopolysaccharidosis IVA (Morquio A syndrome): A review and classification of GALNS gene variants and reporting of 68 novel variants.

Zanetti A, D'Avanzo F, AlSayed M, Brusius-Facchin AC, Chien YH, Giugliani R, Izzo E, Kasper DC, Lin HY, Lin SP, Pollard L, Singh A, Tonin R, Wood T, Morrone A, Tomanin R.

Hum Mutat. 2021 Nov;42(11):1384-1398. doi: 10.1002/humu.24270. Epub 2021 Aug 23. Review.

PubMed [citation]

PMID:: 34387910
PMCID:: PMC9291100

See all PubMed Citations (7)

Details of each submission

From OMIM, SCV000020889.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In a patient with severe Morquio disease (253000), Tomatsu et al. (1995) identified compound heterozygosity for 2 mutations in exon 13 of the GALNS gene: a C-to-T transition resulting in a gln473-to-ter (Q473X) substitution, and an A-to-G transition resulting in an asn487-to-ser substitution (N487S; 612222.0007).

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

From Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova, SCV001547962.3

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

Description

Nonsense variant (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); absent from gnomAD v2.1.1 (PM2_moderate)

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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003443641.3

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

Description

This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with mucopolysaccharidosis type IVA (PMID: 7581409, 33752727). ClinVar contains an entry for this variant (Variation ID: 704). For these reasons, this variant has been classified as Pathogenic. This sequence change creates a premature translational stop signal (p.Gln473*) in the GALNS gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in GALNS are known to be pathogenic (PMID: 12442278).

#	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: May 16, 2025

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