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 GnomAD (PM2)
ClinVar Genomic variation as it relates to human health
NM_000046.5(ARSB):c.479G>A (p.Arg160Gln)
Germline
Classification
Help
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
(5)
Help
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
Pathogenic/Likely pathogenic
5
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_000046.5(ARSB):c.479G>A (p.Arg160Gln)
Variation ID: 445292 Accession: VCV000445292.11
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 5q14.1 5: 78969026 (GRCh38) [ NCBI UCSC ] 5: 78264849 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Jun 2, 2018 Jun 17, 2024 Dec 10, 2023 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000046.5:c.479G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000037.2:p.Arg160Gln missense NM_000046.3:c.479G>A NM_198709.3:c.479G>A NP_942002.1:p.Arg160Gln missense NC_000005.10:g.78969026C>T NC_000005.9:g.78264849C>T NG_007089.1:g.22509G>A - Protein change
- R160Q
- Other names
- -
- Canonical SPDI
- NC_000005.10:78969025:C:T
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
- -
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
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The Genome Aggregation Database (gnomAD), exomes 0.00000
Trans-Omics for Precision Medicine (TOPMed) 0.00000
- Links
Genes
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
|---|---|---|---|---|---|---|
| HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
|||
| ARSB | - | - |
GRCh38 GRCh37 |
720 | 967 | |
Conditions - Germline
| Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
|---|---|---|---|---|
| Pathogenic/Likely pathogenic (5) |
criteria provided, multiple submitters, no conflicts
|
Dec 10, 2023 | RCV000656130.12 |
Submissions - Germline
| Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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|---|---|---|---|---|---|
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Pathogenic
(Dec 01, 2015)
|
criteria provided, single submitter
Method: research
|
Mucopolysaccharidosis type 6
Affected status: yes
Allele origin:
germline
|
Medical Molecular Genetics Department, National Research Center
Accession: SCV000609484.1
First in ClinVar: Jun 02, 2018 Last updated: Jun 02, 2018
Comment:
Homozygous
|
Number of individuals with the variant: 1
Sex: male
Geographic origin: North Africa/Egypt
|
|
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Likely pathogenic
(Jan 01, 2018)
|
criteria provided, single submitter
Method: curation
|
Mucopolysaccharidosis type 6
Affected status: yes
Allele origin:
germline
|
Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova
Accession: SCV000803084.1
First in ClinVar: Jun 02, 2018 Last updated: Jun 02, 2018 |
Comment:
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 … (more)
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 GnomAD (PM2) (less)
|
|
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Pathogenic
(May 24, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Mucopolysaccharidosis type 6
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV001586727.4
First in ClinVar: May 10, 2021 Last updated: Feb 14, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, … (more)
For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ARSB protein function. ClinVar contains an entry for this variant (Variation ID: 445292). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 160 of the ARSB protein (p.Arg160Gln). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This missense change has been observed in individual(s) with mucopolysaccharidosis type VI (PMID: 8125475, 17643332, 22133300, 24677745, 27797586). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. (less)
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Pathogenic
(Aug 07, 2023)
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criteria provided, single submitter
Method: clinical testing
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Mucopolysaccharidosis type 6
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV004038262.1
First in ClinVar: Oct 07, 2023 Last updated: Oct 07, 2023 |
Comment:
Variant summary: ARSB c.479G>A (p.Arg160Gln) results in a conservative amino acid change located in the sulfatase, N-terminal domain (IPR000917) of the encoded protein sequence. Four … (more)
Variant summary: ARSB c.479G>A (p.Arg160Gln) results in a conservative amino acid change located in the sulfatase, N-terminal domain (IPR000917) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251478 control chromosomes (gnomAD). c.479G>A has been reported in the literature as a biallelic genotype in multiple individuals affected with Mucopolysaccharidosis Type VI (Maroteaux-Lamy Syndrome) (e.g. Voskoboeva_1994, Garrido_2007, Kantaputra_2014, Fang_2022). These data indicate that the variant is very likely to be associated with disease. The following publications have been ascertained in the context of this evaluation (PMID: 34813777, 17643332, 22133300, 24677745, 8125475). Three submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as pathogenic (n=2)/likely pathogenic (n=1). Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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Pathogenic
(Dec 10, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Mucopolysaccharidosis type 6
Affected status: unknown
Allele origin:
unknown
|
Baylor Genetics
Accession: SCV004209103.2
First in ClinVar: Dec 30, 2023 Last updated: Jun 17, 2024 |
|
Comment:
Comment:
For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ARSB protein function. ClinVar contains an entry for this variant (Variation ID: 445292). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 160 of the ARSB protein (p.Arg160Gln). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This missense change has been observed in individual(s) with mucopolysaccharidosis type VI (PMID: 8125475, 17643332, 22133300, 24677745, 27797586). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant.
Comment:
Variant summary: ARSB c.479G>A (p.Arg160Gln) results in a conservative amino acid change located in the sulfatase, N-terminal domain (IPR000917) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251478 control chromosomes (gnomAD). c.479G>A has been reported in the literature as a biallelic genotype in multiple individuals affected with Mucopolysaccharidosis Type VI (Maroteaux-Lamy Syndrome) (e.g. Voskoboeva_1994, Garrido_2007, Kantaputra_2014, Fang_2022). These data indicate that the variant is very likely to be associated with disease. The following publications have been ascertained in the context of this evaluation (PMID: 34813777, 17643332, 22133300, 24677745, 8125475). Three submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as pathogenic (n=2)/likely pathogenic (n=1). Based on the evidence outlined above, the variant was classified as pathogenic.
Germline Functional Evidence
| There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Comment:
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 GnomAD (PM2)
Comment:
For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ARSB protein function. ClinVar contains an entry for this variant (Variation ID: 445292). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 160 of the ARSB protein (p.Arg160Gln). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This missense change has been observed in individual(s) with mucopolysaccharidosis type VI (PMID: 8125475, 17643332, 22133300, 24677745, 27797586). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant.
Comment:
Variant summary: ARSB c.479G>A (p.Arg160Gln) results in a conservative amino acid change located in the sulfatase, N-terminal domain (IPR000917) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251478 control chromosomes (gnomAD). c.479G>A has been reported in the literature as a biallelic genotype in multiple individuals affected with Mucopolysaccharidosis Type VI (Maroteaux-Lamy Syndrome) (e.g. Voskoboeva_1994, Garrido_2007, Kantaputra_2014, Fang_2022). These data indicate that the variant is very likely to be associated with disease. The following publications have been ascertained in the context of this evaluation (PMID: 34813777, 17643332, 22133300, 24677745, 8125475). Three submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as pathogenic (n=2)/likely pathogenic (n=1). Based on the evidence outlined above, the variant was classified as pathogenic.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Molecular analysis and novel variation identification of Chinese pedigrees with mucopolysaccharidosis using targeted next-generation sequencing. | Fang X | Clinica chimica acta; international journal of clinical chemistry | 2022 | PMID: 34813777 |
| Novel Mutations, Including a Large Deletion in the ARSB Gene, Causing Mucopolysaccharidosis Type VI. | Ittiwut C | Genetic testing and molecular biomarkers | 2017 | PMID: 27797586 |
| Mutations in ARSB in MPS VI patients in India. | Mathew J | Molecular genetics and metabolism reports | 2015 | PMID: 26937411 |
| Clinical manifestations of 17 patients affected with mucopolysaccharidosis type VI and eight novel ARSB mutations. | Kantaputra PN | American journal of medical genetics. Part A | 2014 | PMID: 24677745 |
| Mucopolysaccharidosis type VI in Russia, Kazakhstan, and Central and Eastern Europe. | Jurecka A | Pediatrics international : official journal of the Japan Pediatric Society | 2014 | PMID: 24373060 |
| Molecular analysis of mucopolysaccharidosis type VI in Poland, Belarus, Lithuania and Estonia. | Jurecka A | Molecular genetics and metabolism | 2012 | PMID: 22133300 |
| Identification of the molecular defects in Spanish and Argentinian mucopolysaccharidosis VI (Maroteaux-Lamy syndrome) patients, including 9 novel mutations. | Garrido E | Molecular genetics and metabolism | 2007 | PMID: 17643332 |
| Mutational analysis of 105 mucopolysaccharidosis type VI patients. | Karageorgos L | Human mutation | 2007 | PMID: 17458871 |
| [Identification of mutations in the arylsulfatase B gene in Russian mucopolysaccharidosis type VI patients]. | Voskoboeva EIu | Genetika | 2000 | PMID: 10923267 |
| Four novel mutant alleles of the arylsulfatase B gene in two patients with intermediate form of mucopolysaccharidosis VI (Maroteaux-Lamy syndrome). | Voskoboeva E | Human genetics | 1994 | PMID: 8125475 |
Text-mined citations for rs1196325597 ...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record last updated Sep 29, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.