ClinVar Genomic variation as it relates to human health
NM_015559.3(SETBP1):c.1765C>T (p.Arg589Ter)
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_015559.3(SETBP1):c.1765C>T (p.Arg589Ter)
Variation ID: 620410 Accession: VCV000620410.13
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 18q12.3 18: 44951105 (GRCh38) [ NCBI UCSC ] 18: 42531070 (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 Mar 19, 2019 Feb 20, 2024 Apr 18, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_015559.3:c.1765C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_056374.2:p.Arg589Ter nonsense NC_000018.10:g.44951105C>T NC_000018.9:g.42531070C>T NG_027527.2:g.275933C>T LRG_1150:g.275933C>T LRG_1150t1:c.1765C>T LRG_1150p1:p.Arg589Ter - Protein change
- R589*
- Other names
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- Canonical SPDI
- NC_000018.10:44951104: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
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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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SETBP1 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
1449 | 1495 |
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
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
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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 (5) |
criteria provided, multiple submitters, no conflicts
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Apr 18, 2023 | RCV000760784.15 | |
Likely pathogenic (1) |
no assertion criteria provided
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Nov 17, 2017 | RCV001265285.8 | |
not provided (1) |
no classification provided
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- | RCV001816816.9 |
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
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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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Pathogenic
(Sep 15, 2021)
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criteria provided, single submitter
Method: clinical testing
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not provided
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
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Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen
Accession: SCV001905588.1
First in ClinVar: Sep 25, 2021 Last updated: Sep 25, 2021 |
Clinical Features:
Autism (present) , Short attention span (present) , Hyperactivity (present) , Absent speech (present) , Profound global developmental delay (present)
Sex: male
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Pathogenic
(Apr 18, 2023)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000890679.2
First in ClinVar: Mar 19, 2019 Last updated: Apr 30, 2023 |
Comment:
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of … (more)
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 28487787, 33391157, 33907317) (less)
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Pathogenic
(Sep 27, 2022)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV003315167.2
First in ClinVar: Feb 07, 2023 Last updated: Feb 20, 2024 |
Comment:
ClinVar contains an entry for this variant (Variation ID: 620410). For these reasons, this variant has been classified as Pathogenic. This premature translational stop signal … (more)
ClinVar contains an entry for this variant (Variation ID: 620410). For these reasons, this variant has been classified as Pathogenic. This premature translational stop signal has been observed in individual(s) with intellectual disability (PMID: 33391157). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg589*) in the SETBP1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SETBP1 are known to be pathogenic (PMID: 21037274, 25217958). (less)
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Likely pathogenic
(Nov 17, 2017)
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no assertion criteria provided
Method: provider interpretation
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Intellectual disability, autosomal dominant 29
Affected status: yes
Allele origin:
de novo
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GenomeConnect - Simons Searchlight
Accession: SCV001443402.1
First in ClinVar: Nov 21, 2020 Last updated: Nov 21, 2020 |
Comment:
Submission from Simons Searchlight facilitated by GenomeConnect. Variant interpreted by the Simons Searchlight team most recently on 2017-11-17 and interpreted as Likely Pathogenic. Variant was … (more)
Submission from Simons Searchlight facilitated by GenomeConnect. Variant interpreted by the Simons Searchlight team most recently on 2017-11-17 and interpreted as Likely Pathogenic. Variant was initially reported on 2015-05-13 by GTR ID of laboratory name North East Thames Genetic Service. The reporting laboratory might also submit to ClinVar. (less)
Clinical Features:
Poor suck (present) , Feeding difficulties in infancy (present) , Generalized hypotonia (present) , Gastroesophageal reflux (present)
Age: 10-19 years
Sex: male
Testing laboratory: North East Thames Genetic Service
Date variant was reported to submitter: 2015-05-13
Testing laboratory interpretation: Likely pathogenic
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Genome Diagnostics Laboratory, Amsterdam University Medical Center
Study: VKGL Data-share Consensus
Accession: SCV001809387.1 First in ClinVar: Aug 25, 2021 Last updated: Aug 25, 2021 |
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001743546.3 First in ClinVar: Jul 07, 2021 Last updated: Sep 08, 2021 |
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not provided
(-)
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no classification provided
Method: phenotyping only
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Intellectual disability, autosomal dominant 29
Schinzel-Giedion syndrome
Explanation for multiple conditions: Uncertain.
The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases.
Affected status: yes
Allele origin:
unknown
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GenomeConnect - Brain Gene Registry
Accession: SCV002064263.2
First in ClinVar: Jan 29, 2022 Last updated: Jun 17, 2023 |
Comment:
Variant reported in multiple GenomeConnect participants by GeneDx. Variant interpreted as Pathogenic and reported, most recently, on 04-29-2020 as well as on 11-14-2018. Assertions are … (more)
Variant reported in multiple GenomeConnect participants by GeneDx. Variant interpreted as Pathogenic and reported, most recently, on 04-29-2020 as well as on 11-14-2018. Assertions are reported exactly as they appear on the patient provided laboratory report. GenomeConnect does not attempt to reinterpret the variant. The IDDRC-CTSA National Brain Gene Registry (BGR) is a study funded by the U.S. National Center for Advancing Translational Sciences (NCATS) and includes 13 Intellectual and Developmental Disability Research Center (IDDRC) institutions. The study is led by Principal Investigator Dr. Philip Payne?from Washington University. The BGR is a data commons of gene variants paired with subject clinical information. This database helps scientists learn more about genetic changes and their impact on the brain and behavior. Participation in the Brain Gene Registry requires participation in GenomeConnect. More information about the Brain Gene Registry can be found on the study website - https://braingeneregistry.wustl.edu/. (less)
Clinical Features:
Abnormality of eye movement (present) , Cognitive impairment (present) , Abnormality of coordination (present) , Generalized hypotonia (present) , Anxiety (present) , Abnormal muscle physiology … (more)
Abnormality of eye movement (present) , Cognitive impairment (present) , Abnormality of coordination (present) , Generalized hypotonia (present) , Anxiety (present) , Abnormal muscle physiology (present) (less)
Indication for testing: Diagnostic
Age: 0-9 years
Sex: female
Method: Gene Panel Sequencing
Testing laboratory: GeneDx
Date variant was reported to submitter: 2020-04-29
Testing laboratory interpretation: Pathogenic
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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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Identification of SETBP1 Mutations by Gene Panel Sequencing in Individuals With Intellectual Disability or With "Developmental and Epileptic Encephalopathy". | Leonardi E | Frontiers in neurology | 2020 | PMID: 33391157 |
Refining analyses of copy number variation identifies specific genes associated with developmental delay. | Coe BP | Nature genetics | 2014 | PMID: 25217958 |
Reduced expression by SETBP1 haploinsufficiency causes developmental and expressive language delay indicating a phenotype distinct from Schinzel-Giedion syndrome. | Filges I | Journal of medical genetics | 2011 | PMID: 21037274 |
Text-mined citations for rs1568235086 ...
HelpRecord last updated Apr 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.