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

Clinical significance:Pathogenic/Likely pathogenic (Last evaluated: Jul 22, 2021)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
3 submissions [Details]
Record status:
current
Accession:
RCV000677562.4

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:
MPS VI; Mucopolysaccharidosis type VI; MPS 6; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0009661; MedGen: C0026709; Orphanet: 583; OMIM: 253200

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000803075Laboratory of Diagnosis and Therapy of Lysosomal Disorders,University of Padovacriteria provided, single submitter
Likely pathogenic
(Jan 1, 2018)
germlinecuration

PubMed (7)
[See all records that cite these PMIDs]

SCV001225796Invitaecriteria provided, single submitter
Pathogenic
(Nov 28, 2019)
germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

SCV001810267Nilou-Genome Labcriteria provided, single submitter
Likely pathogenic
(Jul 22, 2021)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenonot providednot providednot providednot providednot providedclinical testing
not providedgermlineyesnot providednot providednot providednot providednot providedcuration
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcuration 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)

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

From Invitae, SCV001225796.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

This sequence change replaces glycine with arginine at codon 144 of the ARSB protein (p.Gly144Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is present in population databases (rs746206847, ExAC 0.02%). This variant has been observed in individual(s) with mucopolysaccharidosis type VI (PMID: 8116615, 30982216, 16435196, 26909334). ClinVar contains an entry for this variant (Variation ID: 559783). This variant has been reported to affect ARSB protein function (PMID: 8116615). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. For these reasons, this variant has been classified as Pathogenic.

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

From Nilou-Genome Lab, SCV001810267.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenonot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 27, 2021

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