NM_000046.5(ARSB):c.574T>C (p.Cys192Arg) AND Mucopolysaccharidosis type 6

Clinical significance:Pathogenic/Likely pathogenic (Last evaluated: Jan 15, 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:
RCV000677578.3

Allele description [Variation Report for NM_000046.5(ARSB):c.574T>C (p.Cys192Arg)]

NM_000046.5(ARSB):c.574T>C (p.Cys192Arg)

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.574T>C (p.Cys192Arg)
HGVS:
  • NC_000005.10:g.78964532A>G
  • NG_007089.1:g.27003T>C
  • NM_000046.5:c.574T>CMANE SELECT
  • NM_198709.3:c.574T>C
  • NP_000037.2:p.Cys192Arg
  • NP_942002.1:p.Cys192Arg
  • NC_000005.9:g.78260355A>G
  • NM_000046.3:c.574T>C
  • NM_000046.4:c.574T>C
Protein change:
C192R
Links:
dbSNP: rs1554087423
NCBI 1000 Genomes Browser:
rs1554087423
Molecular consequence:
  • NM_000046.5:c.574T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_198709.3:c.574T>C - 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
SCV000803094Laboratory of Diagnosis and Therapy of Lysosomal Disorders,University of Padovacriteria provided, single submitter
Likely pathogenic
(Jan 1, 2018)
germlinecuration

PubMed (10)
[See all records that cite these PMIDs]

SCV001235859Invitaecriteria provided, single submitter
Pathogenic
(Jan 15, 2020)
germlineclinical testing

PubMed (4)
[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

A pilot newborn screening program for Mucopolysaccharidosis type I in Taiwan.

Lin SP, Lin HY, Wang TJ, Chang CY, Lin CH, Huang SF, Tsai CC, Liu HL, Keutzer J, Chuang CK.

Orphanet J Rare Dis. 2013 Sep 22;8:147. doi: 10.1186/1750-1172-8-147.

PubMed [citation]
PMID:
24053568
PMCID:
PMC3849552

Clinical characteristics of adults with slowly progressing mucopolysaccharidosis VI: a case series.

Th├╝mler A, Miebach E, Lampe C, Pitz S, Kamin W, Kampmann C, Link B, Mengel E.

J Inherit Metab Dis. 2012 Nov;35(6):1071-9. doi: 10.1007/s10545-012-9474-1. Epub 2012 Mar 23.

PubMed [citation]
PMID:
22441840
See all PubMed Citations (11)

Details of each submission

From Laboratory of Diagnosis and Therapy of Lysosomal Disorders,University of Padova, SCV000803094.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcuration PubMed (10)

Description

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

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

From Invitae, SCV001235859.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

This sequence change replaces cysteine with arginine at codon 192 of the ARSB protein (p.Cys192Arg). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with mucopolysaccharidosis VI (PMID: 17458871, 8116615, 24107440). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 559798). This variant has been reported to affect ARSB protein function (PMID: 8116615). 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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