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

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 2, 2017
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:: RCV000779747.9

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_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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000916522	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (Nov 2, 2017)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 23557332, 21514195, 17458871 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000916522

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

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Pathogenic
(Nov 2, 2017)

germline

clinical testing

PubMed (3)
[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 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

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical 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.

#	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: Nov 10, 2024

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