NM_000512.5(GALNS):c.331C>T (p.Gln111Ter) AND Morquio syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 27, 2020
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:: RCV001193733.2

Allele description [Variation Report for NM_000512.5(GALNS):c.331C>T (p.Gln111Ter)]

NM_000512.5(GALNS):c.331C>T (p.Gln111Ter)

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.331C>T (p.Gln111Ter)

HGVS:

NC_000016.10:g.88841083G>A
NG_008667.1:g.20884C>T
NM_000512.5:c.331C>TMANE SELECT
NM_001323543.2:c.-225C>T
NM_001323544.2:c.349C>T
NP_000503.1:p.Gln111Ter
NP_001310473.1:p.Gln117Ter
NC_000016.9:g.88907491G>A
NM_000512.4:c.331C>T

Protein change:

Q111*

Links:

dbSNP: rs200374326

NCBI 1000 Genomes Browser:

rs200374326

Molecular consequence:

NM_001323543.2:c.-225C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000512.5:c.331C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001323544.2:c.349C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Morquio syndrome
Synonyms:: Mucopolysaccharidosis, Type IV; MPS IV; Mucopolysaccharidosis type 4; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0018938; MedGen: C0026707; Orphanet: 582

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001362795	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (Jul 27, 2020)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 24726177, 16287098 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001362795

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Pathogenic
(Jul 27, 2020)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

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

Molecular testing of 163 patients with Morquio A (Mucopolysaccharidosis IVA) identifies 39 novel GALNS mutations.

Morrone A, Tylee KL, Al-Sayed M, Brusius-Facchin AC, Caciotti A, Church HJ, Coll MJ, Davidson K, Fietz MJ, Gort L, Hegde M, Kubaski F, Lacerda L, Laranjeira F, Leistner-Segal S, Mooney S, Pajares S, Pollard L, Ribeiro I, Wang RY, Miller N.

Mol Genet Metab. 2014 Jun;112(2):160-70. doi: 10.1016/j.ymgme.2014.03.004. Epub 2014 Mar 20. Erratum in: Mol Genet Metab. 2014 Nov;113(3):237.

PubMed [citation]

PMID:: 24726177
PMCID:: PMC4203673

Mutation and polymorphism spectrum of the GALNS gene in mucopolysaccharidosis IVA (Morquio A).

Tomatsu S, Montaño AM, Nishioka T, Gutierrez MA, Peña OM, Tranda Firescu GG, Lopez P, Yamaguchi S, Noguchi A, Orii T.

Hum Mutat. 2005 Dec;26(6):500-12.

PubMed [citation]

PMID:: 16287098

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001362795.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

Variant summary: GALNS c.331C>T (p.Gln111X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 1.6e-05 in 250768 control chromosomes. c.331C>T has been reported in the literature in individuals affected with Mucopolysaccharidosis Type IVA (Morquio Syndrome A) and subsequently cited by others (example, Tomatsu_2005, Morrone_2014). These data indicate that the variant is very likely associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as pathogenic. Based on the evidence outlined above, the variant was 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: Sep 29, 2024

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