NM_000512.5(GALNS):c.901G>T (p.Gly301Cys) AND Morquio syndrome

Clinical significance:Pathogenic (Last evaluated: Apr 24, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000781400.1

Allele description [Variation Report for NM_000512.5(GALNS):c.901G>T (p.Gly301Cys)]

NM_000512.5(GALNS):c.901G>T (p.Gly301Cys)

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.901G>T (p.Gly301Cys)
HGVS:
  • NC_000016.10:g.88832099C>A
  • NG_008667.1:g.29868G>T
  • NM_000512.5:c.901G>TMANE SELECT
  • NM_001323543.2:c.346G>T
  • NM_001323544.2:c.919G>T
  • NP_000503.1:p.Gly301Cys
  • NP_000503.1:p.Gly301Cys
  • NP_000503.1:p.Gly301Cys
  • NP_001310472.1:p.Gly116Cys
  • NP_001310473.1:p.Gly307Cys
  • NC_000016.9:g.88898507C>A
  • NM_000512.4:c.901G>T
  • P34059:p.Gly301Cys
Protein change:
G116C; GLY301CYS
Links:
UniProtKB: P34059#VAR_007216; OMIM: 612222.0010; dbSNP: rs118204443
NCBI 1000 Genomes Browser:
rs118204443
Molecular consequence:
  • NM_000512.5:c.901G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001323543.2:c.346G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001323544.2:c.919G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000919397Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Pathogenic
(Apr 24, 2018)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

A novel common missense mutation G301C in the N-acetylgalactosamine-6-sulfate sulfatase gene in mucopolysaccharidosis IVA.

Kato Z, Fukuda S, Tomatsu S, Vega H, Yasunaga T, Yamagishi A, Yamada N, Valencia A, Barrera LA, Sukegawa K, Orii T, Kondo N.

Hum Genet. 1997 Nov;101(1):97-101.

PubMed [citation]
PMID:
9385378

Identification of 31 novel mutations in the N-acetylgalactosamine-6-sulfatase gene reveals excessive allelic heterogeneity among patients with Morquio A syndrome.

Bunge S, Kleijer WJ, Tylki-Szymanska A, Steglich C, Beck M, Tomatsu S, Fukuda S, Poorthuis BJ, Czartoryska B, Orii T, Gal A.

Hum Mutat. 1997;10(3):223-32.

PubMed [citation]
PMID:
9298823
See all PubMed Citations (3)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000919397.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

Variant summary: GALNS c.901G>T (p.Gly301Cys) results in a non-conservative amino acid change located in the sulfatase, N-terminal domain (IPR000917) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00011 in 111042 control chromosomes (gnomAD). This frequency is not higher than expected for a pathogenic variant in GALNS causing Mucopolysaccharidosis Type IVA (Morquio Syndrome A) (0.00011 vs 0.002), allowing no conclusion about variant significance. The variant, c.901G>T has been reported in the literature in multiple individuals affected with Mucopolysaccharidosis Type IVA (Morquio Syndrome A) (e.g. Kato 1997, Bunge 1997, Dung 2013). These data indicate that the variant is very likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in <10% of normal activity (Kato 1997). 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 16, 2021

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