NM_000046.5(ARSB):c.113del (p.Gly38fs) AND Mucopolysaccharidosis type 6

Germline classification:: Pathogenic/Likely pathogenic (3 submissions)
Last evaluated:: Jan 1, 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:: RCV001382525.10

Allele description [Variation Report for NM_000046.5(ARSB):c.113del (p.Gly38fs)]

NM_000046.5(ARSB):c.113del (p.Gly38fs)

Genes:

LOC129994126:ATAC-STARR-seq lymphoblastoid silent region 16127 [Gene]
ARSB:arylsulfatase B [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

5q14.1

Genomic location:

Preferred name:

NM_000046.5(ARSB):c.113del (p.Gly38fs)

HGVS:

NC_000005.10:g.78985138del
NG_007089.1:g.6399del
NM_000046.5:c.113delMANE SELECT
NM_198709.3:c.113del
NP_000037.2:p.Gly38fs
NP_942002.1:p.Gly38fs
NC_000005.9:g.78280959del
NC_000005.9:g.78280961del
NM_000046.5:c.113delGMANE SELECT

Protein change:

G38fs

Links:

dbSNP: rs1349838988

NCBI 1000 Genomes Browser:

rs1349838988

Molecular consequence:

NM_000046.5:c.113del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_198709.3:c.113del - frameshift variant - [Sequence Ontology: SO:0001589]

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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001581348	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 22, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 22133300, 17458871, 28492532
SCV004209081	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jan 1, 2024)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004812789	Molecular Genetics, Royal Melbourne Hospital See additional submitters Shariant Australia, Australian Genomics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (May 5, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 17458871, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001581348

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 22, 2023)

germline

clinical testing

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

SCV004209081

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jan 1, 2024)

unknown

clinical testing

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

SCV004812789

Molecular Genetics, Royal Melbourne Hospital

See additional submitters

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(May 5, 2023)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

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

Citations

PubMed

Molecular analysis of mucopolysaccharidosis type VI in Poland, Belarus, Lithuania and Estonia.

Jurecka A, Piotrowska E, Cimbalistiene L, Gusina N, Sobczyńska A, Czartoryska B, Czerska K, Õunap K, Węgrzyn G, Tylki-Szymańska A.

Mol Genet Metab. 2012 Feb;105(2):237-43. doi: 10.1016/j.ymgme.2011.11.003. Epub 2011 Nov 11.

PubMed [citation]

PMID:: 22133300

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group, Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001581348.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change creates a premature translational stop signal (p.Gly38Alafs*18) in the ARSB gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ARSB are known to be pathogenic (PMID: 17458871, 22133300). This variant is present in population databases (no rsID available, gnomAD 0.007%). This premature translational stop signal has been observed in individual(s) with mucopolysaccharidosis type VI (PMID: 17458871). This variant is also known as c.114delG. ClinVar contains an entry for this variant (Variation ID: 1070404). 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 Baylor Genetics, SCV004209081.2

#	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

From Molecular Genetics, Royal Melbourne Hospital, SCV004812789.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change in ARSB is a frameshift variant predicted to cause a premature stop codon, p.(Gly38Alafs*18), in biologically relevant exon 1/8 leading to nonsense-mediated decay in a gene in which loss-of-function is an established disease mechanism (PMID: 17458871). The highest population minor allele frequency in the population database gnomAD v3.1 is 0.003% (2/67,888 alleles) in the European (non-Finnish) population, which is consistent with Mucopolysaccharidosis type VI. To our knowledge, this variant is novel and has not been previously reported in the relevant scientific literature. Based on the classification scheme RMH Modified ACMG/AMP Guidelines v1.6.1, this variant is classified as LIKELY PATHOGENIC. Following criteria are met: PVS1, PM2_Supporting.

#	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

Last Updated: Sep 29, 2024

ClinVar

Relating variation to medicine