NM_000046.5(ARSB):c.937C>G (p.Pro313Ala) AND Mucopolysaccharidosis type 6

Clinical significance:Pathogenic/Likely pathogenic (Last evaluated: Aug 25, 2020)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000677609.2

Allele description [Variation Report for NM_000046.5(ARSB):c.937C>G (p.Pro313Ala)]

NM_000046.5(ARSB):c.937C>G (p.Pro313Ala)

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.937C>G (p.Pro313Ala)
HGVS:
  • NC_000005.10:g.78885789G>C
  • NG_007089.1:g.105746C>G
  • NM_000046.5:c.937C>GMANE SELECT
  • NM_198709.3:c.937C>G
  • NP_000037.2:p.Pro313Ala
  • NP_942002.1:p.Pro313Ala
  • NC_000005.9:g.78181612G>C
  • NM_000046.4:c.937C>G
Protein change:
P313A
Links:
dbSNP: rs749989641
NCBI 1000 Genomes Browser:
rs749989641
Molecular consequence:
  • NM_000046.5:c.937C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_198709.3:c.937C>G - 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
SCV000803126Laboratory 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]

SCV001586724Invitaecriteria provided, single submitter
Pathogenic
(Aug 25, 2020)
germlineclinical testing

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

Summary from all submissions

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

Citations

PubMed

Maroteaux-Lamy syndrome: functional characterization of pathogenic mutations and polymorphisms in the arylsulfatase B gene.

Garrido E, Cormand B, Hopwood JJ, Chabás A, Grinberg D, Vilageliu L.

Mol Genet Metab. 2008 Jul;94(3):305-12. doi: 10.1016/j.ymgme.2008.02.012. Epub 2008 Apr 10.

PubMed [citation]
PMID:
18406185

A long term follow-up study of the development of hip disease in Mucopolysaccharidosis type VI.

Oussoren E, Bessems JHJM, Pollet V, van der Meijden JC, van der Giessen LJ, Plug I, Devos AS, Ruijter GJG, van der Ploeg AT, Langeveld M.

Mol Genet Metab. 2017 Jul;121(3):241-251. doi: 10.1016/j.ymgme.2017.05.008. Epub 2017 May 19.

PubMed [citation]
PMID:
28552677
See all PubMed Citations (10)

Details of each submission

From Laboratory of Diagnosis and Therapy of Lysosomal Disorders,University of Padova, SCV000803126.1

#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); Multiple lines of computational evidence support a deleterious effect on the gene product (PP3); Reputable source identifies as pathogenic (PP5)

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

From Invitae, SCV001586724.1

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

Description

This sequence change replaces proline with alanine at codon 313 of the ARSB protein (p.Pro313Ala). The proline residue is highly conserved and there is a small physicochemical difference between proline and alanine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with mucolipidosis VI (PMID: 17458871, 17643332, 23557332). ClinVar contains an entry for this variant (Variation ID: 559826). This variant has been reported to affect ARSB protein function (PMID: 27826022). For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Nov 27, 2021

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