NM_000512.5(GALNS):c.938C>T (p.Thr313Met) AND Morquio syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 11, 2023
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:: RCV003331131.1

Allele description [Variation Report for NM_000512.5(GALNS):c.938C>T (p.Thr313Met)]

NM_000512.5(GALNS):c.938C>T (p.Thr313Met)

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.938C>T (p.Thr313Met)

Other names:

p.Thr313Met

HGVS:

NC_000016.10:g.88832062G>A
NG_008667.1:g.29905C>T
NM_000512.5:c.938C>TMANE SELECT
NM_001323543.2:c.383C>T
NM_001323544.2:c.956C>T
NP_000503.1:p.Thr313Met
NP_001310472.1:p.Thr128Met
NP_001310473.1:p.Thr319Met
NC_000016.9:g.88898470G>A
NM_000512.4:c.938C>T
NM_001323544.2:c.956C>T

Protein change:

T128M

Links:

dbSNP: rs894525161

NCBI 1000 Genomes Browser:

rs894525161

Molecular consequence:

NM_000512.5:c.938C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001323543.2:c.383C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001323544.2:c.956C>T - missense variant - [Sequence Ontology: SO:0001583]

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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004039050	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (Aug 11, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 23876334, 25252036, 34387910, 32993725 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004039050

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

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Pathogenic
(Aug 11, 2023)

germline

clinical testing

PubMed (4)
[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

Mucopolysaccharidosis IVA: correlation between genotype, phenotype and keratan sulfate levels.

Dũng VC, Tomatsu S, Montaño AM, Gottesman G, Bober MB, Mackenzie W, Maeda M, Mitchell GA, Suzuki Y, Orii T.

Mol Genet Metab. 2013 Sep-Oct;110(1-2):129-38. doi: 10.1016/j.ymgme.2013.06.008. Epub 2013 Jun 26.

PubMed [citation]

PMID:: 23876334
PMCID:: PMC3779837

GALNS mutations in Indian patients with mucopolysaccharidosis IVA.

Bidchol AM, Dalal A, Shah H, S S, Nampoothiri S, Kabra M, Gupta N, Danda S, Gowrishankar K, Phadke SR, Kapoor S, Kamate M, Verma IC, Puri RD, Sankar VH, Devi AR, Patil SJ, Ranganath P, Jain SJ, Agarwal M, Singh A, Mishra P, et al.

Am J Med Genet A. 2014 Nov;164A(11):2793-801. doi: 10.1002/ajmg.a.36735. Epub 2014 Sep 22.

PubMed [citation]

PMID:: 25252036

See all PubMed Citations (4)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV004039050.1

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

Description

Variant summary: GALNS c.938C>T (p.Thr313Met) 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 1.6e-05 in 250640 control chromosomes (gnomAD). c.938C>T has been reported in the literature in multiple individuals affected with Mucopolysaccharidosis Type IVA (Morquio Syndrome A) (e.g. Dung_2013, Bidchol_2014, Moisan_2020, Zanetti_2021) . These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 25252036, 23876334, 32993725, 34387910). Four submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as pathogenic/likely 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

ClinVar

Relating variation to medicine