NM_000046.5(ARSB):c.430G>A (p.Gly144Arg) AND Mucopolysaccharidosis type 6

Germline classification:: Pathogenic/Likely pathogenic (5 submissions)
Last evaluated:: Apr 15, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000677562.15

Allele description [Variation Report for NM_000046.5(ARSB):c.430G>A (p.Gly144Arg)]

NM_000046.5(ARSB):c.430G>A (p.Gly144Arg)

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.430G>A (p.Gly144Arg)

HGVS:

NC_000005.10:g.78969075C>T
NG_007089.1:g.22460G>A
NM_000046.5:c.430G>AMANE SELECT
NM_198709.3:c.430G>A
NP_000037.2:p.Gly144Arg
NP_942002.1:p.Gly144Arg
NC_000005.9:g.78264898C>T
NM_000046.3:c.430G>A
NM_000046.4:c.430G>A

Protein change:

G144R

Links:

dbSNP: rs746206847

NCBI 1000 Genomes Browser:

rs746206847

Molecular consequence:

NM_000046.5:c.430G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_198709.3:c.430G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Mucopolysaccharidosis type 6 (MPS6)
Synonyms:: ARSB DEFICIENCY; ARYLSULFATASE B DEFICIENCY; MPS VI; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009661; MedGen: C0026709; Orphanet: 583; OMIM: 253200

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000803075	Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Jan 1, 2018)	germline	curation	PubMed (7) [See all records that cite these PMIDs] 26909334, 8116615, 17458871, 24875751, 16435196, 25741868, 30118150
SCV001225796	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Apr 15, 2024)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 16435196, 26909334, 30982216, 8116615, 28492532
SCV001810267	Genome-Nilou Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Jul 22, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002084982	Natera, Inc.	no assertion criteria provided	Pathogenic (Sep 4, 2020)	germline	clinical testing
SCV004209192	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 8, 2024)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

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
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	curation
not provided	germline	no	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutational analysis of 105 mucopolysaccharidosis type VI patients.

Karageorgos L, Brooks DA, Pollard A, Melville EL, Hein LK, Clements PR, Ketteridge D, Swiedler SJ, Beck M, Giugliani R, Harmatz P, Wraith JE, Guffon N, Leão Teles E, Sá Miranda MC, Hopwood JJ.

Hum Mutat. 2007 Sep;28(9):897-903.

PubMed [citation]

PMID:: 17458871

Molecular characteristics of patients with glycosaminoglycan storage disorders in Russia.

Chistiakov DA, Savost'anov KV, Kuzenkova LM, Gevorkyan AK, Pushkov AA, Nikitin AG, Pakhomov AV, Vashakmadze ND, Zhurkova NV, Podkletnova TV, Mayansky NA, Namazova-Baranova LS, Baranov AA.

Clin Chim Acta. 2014 Sep 25;436:112-20. doi: 10.1016/j.cca.2014.05.010. Epub 2014 May 26.

PubMed [citation]

PMID:: 24875751

See all PubMed Citations (9)

Details of each submission

From Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova, SCV000803075.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	PubMed (7)

Description

In vitro functional studies supportive of a damaging effect on the gene product (low to no ARSB activity in homozygotes; PS3); Very low frequency in ExAC (PM2)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001225796.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 144 of the ARSB protein (p.Gly144Arg). This variant is present in population databases (rs746206847, gnomAD 0.004%). This missense change has been observed in individual(s) with mucopolysaccharidosis type VI (PMID: 8116615, 16435196, 26909334, 30982216). ClinVar contains an entry for this variant (Variation ID: 559783). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ARSB protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects ARSB function (PMID: 8116615). For these reasons, this variant has been 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

From Genome-Nilou Lab, SCV001810267.2

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Natera, Inc., SCV002084982.1

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

#	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

From Baylor Genetics, SCV004209192.2

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: May 16, 2025

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