NM_000046.5(ARSB):c.1130G>A (p.Trp377Ter) AND Mucopolysaccharidosis type 6

Clinical significance:Pathogenic/Likely pathogenic (Last evaluated: Jun 18, 2019)

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:
RCV000677451.3

Allele description [Variation Report for NM_000046.5(ARSB):c.1130G>A (p.Trp377Ter)]

NM_000046.5(ARSB):c.1130G>A (p.Trp377Ter)

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.1130G>A (p.Trp377Ter)
HGVS:
  • NC_000005.10:g.78885596C>T
  • NG_007089.1:g.105939G>A
  • NM_000046.5:c.1130G>AMANE SELECT
  • NM_198709.3:c.1130G>A
  • NP_000037.2:p.Trp377Ter
  • NP_942002.1:p.Trp377Ter
  • NC_000005.9:g.78181419C>T
  • NM_000046.3:c.1130G>A
  • NM_000046.4:c.1130G>A
Protein change:
W377*
Links:
dbSNP: rs1554079265
NCBI 1000 Genomes Browser:
rs1554079265
Molecular consequence:
  • NM_000046.5:c.1130G>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_198709.3:c.1130G>A - nonsense - [Sequence Ontology: SO:0001587]

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
SCV000802954Laboratory of Diagnosis and Therapy of Lysosomal Disorders,University of Padovacriteria provided, single submitter
Likely pathogenic
(Jan 1, 2018)
germlinecuration

PubMed (3)
[See all records that cite these PMIDs]

SCV001377701Invitaecriteria provided, single submitter
Pathogenic
(Jun 18, 2019)
germlineclinical testing

PubMed (3)
[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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Mucopolysaccharidosis type VI (MPS VI) and molecular analysis: Review and classification of published variants in the ARSB gene.

Tomanin R, Karageorgos L, Zanetti A, Al-Sayed M, Bailey M, Miller N, Sakuraba H, Hopwood JJ.

Hum Mutat. 2018 Dec;39(12):1788-1802. doi: 10.1002/humu.23613. Epub 2018 Sep 17. Review.

PubMed [citation]
PMID:
30118150
PMCID:
PMC6282714
See all PubMed Citations (5)

Details of each submission

From Laboratory of Diagnosis and Therapy of Lysosomal Disorders,University of Padova, SCV000802954.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcuration PubMed (3)

Description

Nonsense variant (PVS1); Absent from GnomAD (PM2)

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

From Invitae, SCV001377701.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change creates a premature translational stop signal (p.Trp377*) in the ARSB gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with mucopolysaccharidosis type VI (PMID: 17458871). ClinVar contains an entry for this variant (Variation ID: 559677). 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. Loss-of-function variants in ARSB are known to be pathogenic (PMID: 17458871, 22133300). 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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