ClinVar Genomic variation as it relates to human health
NM_000046.5(ARSB):c.943C>T (p.Arg315Ter)
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.
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.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000046.5(ARSB):c.943C>T (p.Arg315Ter)
Variation ID: 559828 Accession: VCV000559828.8
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 5q14.1 5: 78885783 (GRCh38) [ NCBI UCSC ] 5: 78181606 (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 Aug 24, 2018 Feb 14, 2024 Nov 24, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000046.5:c.943C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000037.2:p.Arg315Ter nonsense NM_198709.3:c.943C>T NP_942002.1:p.Arg315Ter nonsense NC_000005.10:g.78885783G>A NC_000005.9:g.78181606G>A NG_007089.1:g.105752C>T - Protein change
- R315*
- Other names
- p.Arg315Ter
- Canonical SPDI
- NC_000005.10:78885782:G:A
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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
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The frequency of the allele represented by this VCV record.
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- Links
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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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. |
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ARSB | - | - |
GRCh38 GRCh37 |
700 | 945 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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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
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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
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic/Likely pathogenic (4) |
criteria provided, multiple submitters, no conflicts
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Nov 24, 2023 | RCV000677611.7 |
Submissions - Germline
Classification
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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
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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
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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
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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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Likely pathogenic
(Jan 01, 2018)
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criteria provided, single submitter
Method: curation
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Mucopolysaccharidosis type 6
Affected status: yes
Allele origin:
germline
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Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova
Accession: SCV000803128.1
First in ClinVar: Aug 24, 2018 Last updated: Aug 24, 2018 |
Comment:
Nonsense variant (PVS1); Very low frequency in ExAC (PM2)
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Pathogenic
(Jan 16, 2023)
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criteria provided, single submitter
Method: clinical testing
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Mucopolysaccharidosis type 6
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics
Accession: SCV002822857.1
First in ClinVar: Jan 21, 2023 Last updated: Jan 21, 2023 |
Comment:
A Homozygous missense variation in exon 5 of the PIGA gene that results in the termination of amino acid chain at codon 315 was detected. … (more)
A Homozygous missense variation in exon 5 of the PIGA gene that results in the termination of amino acid chain at codon 315 was detected. The observed variant c.943C>T (p.Arg315Ter) has not been reported in the 1000 genomes and has MAF of 0.0004% in the gnomAD database. The in silico prediction of the variant are possibly damaging by CADD, DANN, LRT and MutationTaster2. In summary, the variant meets our criteria to be classified as pathogenic. (less)
Clinical Features:
Coarse facial features (present) , Respiratory distress (present) , Short stature (present) , Neuropathic spinal arthropathy (present) , Kyphosis (present)
Age: 0-9 years
Sex: female
Method: DNA was used to perform targeted gene capture using a custom capture kit. Libraries were sequenced to mean >80-100X coverage on Illumina sequencing platform. Sequence obtained were aligned to human references genome using BWA program and analyzed using Picard and GATK-Lite toolkit to identify variants in the targeted genes relevant to clinical indication.
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Pathogenic
(May 15, 2023)
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criteria provided, single submitter
Method: clinical testing
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Mucopolysaccharidosis type 6
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV004209825.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Pathogenic
(Nov 24, 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
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Invitae
Accession: SCV003525877.2
First in ClinVar: Feb 07, 2023 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Arg315*) in the ARSB gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Arg315*) 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 0.0009%). This premature translational stop signal has been observed in individual(s) with mucopolysaccharidosis type VI (PMID: 20143913, 24875751). ClinVar contains an entry for this variant (Variation ID: 559828). For these reasons, this variant has been classified as Pathogenic. (less)
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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. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Prevalence of anti-adeno-associated virus serotype 8 neutralizing antibodies and arylsulfatase B cross-reactive immunologic material in mucopolysaccharidosis VI patient candidates for a gene therapy trial. | Ferla R | Human gene therapy | 2015 | PMID: 25654180 |
Molecular characteristics of patients with glycosaminoglycan storage disorders in Russia. | Chistiakov DA | Clinica chimica acta; international journal of clinical chemistry | 2014 | PMID: 24875751 |
A pilot newborn screening program for Mucopolysaccharidosis type I in Taiwan. | Lin SP | Orphanet journal of rare diseases | 2013 | PMID: 24053568 |
Molecular analysis of mucopolysaccharidosis type VI in Poland, Belarus, Lithuania and Estonia. | Jurecka A | Molecular genetics and metabolism | 2012 | PMID: 22133300 |
Large deletion involving exon 5 of the arylsulfatase B gene caused apparent homozygosity in a mucopolysaccharidosis type VI patient. | Villani GR | Genetic testing and molecular biomarkers | 2010 | PMID: 20143913 |
Molecular markers for the follow-up of enzyme-replacement therapy in mucopolysaccharidosis type VI disease. | Di Natale P | Biotechnology and applied biochemistry | 2008 | PMID: 17672828 |
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 |
Text-mined citations for rs891298440 ...
HelpRecord last updated Feb 20, 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.