NM_000046.5(ARSB):c.629A>G (p.Tyr210Cys) AND Metachromatic leukodystrophy

Clinical significance:Pathogenic (Last evaluated: Nov 2, 2017)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000779747.1

Allele description [Variation Report for NM_000046.5(ARSB):c.629A>G (p.Tyr210Cys)]

NM_000046.5(ARSB):c.629A>G (p.Tyr210Cys)

Gene:
ARSB:arylsulfatase B [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
5q14.1
Genomic location:
Preferred name:
NM_000046.5(ARSB):c.629A>G (p.Tyr210Cys)
HGVS:
  • NC_000005.10:g.78964477T>C
  • NG_007089.1:g.27058A>G
  • NM_000046.5:c.629A>GMANE SELECT
  • NM_198709.3:c.629A>G
  • NP_000037.2:p.Tyr210Cys
  • NP_000037.2:p.Tyr210Cys
  • NP_000037.2:p.Tyr210Cys
  • NP_000037.2:p.Tyr210Cys
  • NP_942002.1:p.Tyr210Cys
  • NC_000005.9:g.78260300T>C
  • NM_000046.3:c.629A>G
  • NM_000046.4:c.629A>G
  • P15848:p.Tyr210Cys
Protein change:
Y210C; TYR210CYS
Links:
UniProtKB: P15848#VAR_007300; OMIM: 611542.0009; dbSNP: rs118203943
NCBI 1000 Genomes Browser:
rs118203943
Molecular consequence:
  • NM_000046.5:c.629A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_198709.3:c.629A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Metachromatic leukodystrophy (MLD)
Synonyms:
Metachromatic leukoencephalopathy; Sulfatide lipidosis; Cerebral sclerosis diffuse metachromatic form; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0018868; MedGen: C0023522; Orphanet: 512; OMIM: 250100

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000916522Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Pathogenic
(Nov 2, 2017)
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

Mucopolysaccharidosis type VI phenotypes-genotypes and antibody response to galsulfase.

Brands MM, Hoogeveen-Westerveld M, Kroos MA, Nobel W, Ruijter GJ, Özkan L, Plug I, Grinberg D, Vilageliu L, Halley DJ, van der Ploeg AT, Reuser AJ.

Orphanet J Rare Dis. 2013 Apr 4;8:51. doi: 10.1186/1750-1172-8-51.

PubMed [citation]
PMID:
23557332
PMCID:
PMC3637222

Attenuated mucopolysaccharidosis type VI (Maroteaux-Lamy syndrome) due to homozygosity for the p.Y210C mutation in the ARSB gene.

Gottwald I, Hughes J, Stewart F, Tylee K, Church H, Jones SA.

Mol Genet Metab. 2011 Jul;103(3):300-2. doi: 10.1016/j.ymgme.2011.03.024. Epub 2011 Apr 7.

PubMed [citation]
PMID:
21514195
See all PubMed Citations (3)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000916522.1

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

Description

Variant summary: The ARSB c.629A>G (p.Tyr210Cys) variant located in the Sulfatase, N-termail (via InterPro) involves the alteration of a conserved nucleotide and 5/5 in silico tools predict a damaging outcome for this variant. A functional study, Brands_2013, supports these predictions by observing the variant to cause a significant decrease in ARSB activity in comparison to wild type. This variant was found in 75/277016 control chromosomes (gnomAD), predominantly observed in the European (Non-Finnish) subpopulation at a frequency of 0.000569 (72/126548), which does not exceed the estimated maximal expected allele frequency of a pathogenic ARSB variant (0.0022361). Multiple publications have cited the variant homozygously and in compound heterozygosity in affected individuals and indicated the variant to be one of the of most common mutations (Karageorgos_2007). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.

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

Last Updated: Oct 24, 2021

Support Center