ClinVar Genomic variation as it relates to human health
NM_032436.4(CHAMP1):c.1489C>T (p.Arg497Ter)
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_032436.4(CHAMP1):c.1489C>T (p.Arg497Ter)
Variation ID: 210050 Accession: VCV000210050.8
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 13q34 13: 114325331 (GRCh38) [ NCBI UCSC ] 13: 115090806 (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 Oct 5, 2015 Mar 11, 2023 Mar 8, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_032436.4:c.1489C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_115812.1:p.Arg497Ter nonsense NM_001164144.3:c.1489C>T NP_001157616.1:p.Arg497Ter nonsense NM_001164145.3:c.1489C>T NP_001157617.1:p.Arg497Ter nonsense NC_000013.11:g.114325331C>T NC_000013.10:g.115090806C>T NG_051829.1:g.15997C>T - Protein change
- R497*
- Other names
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- Canonical SPDI
- NC_000013.11:114325330: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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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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CHAMP1 | Some evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
197 | 316 | |
LINC01054 | - | - | - | GRCh38 | - | 19 |
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 (3) |
criteria provided, multiple submitters, no conflicts
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Mar 8, 2023 | RCV000191999.7 | |
Pathogenic (1) |
criteria provided, single submitter
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Dec 7, 2022 | RCV000599119.2 | |
Pathogenic (1) |
criteria provided, single submitter
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Apr 26, 2017 | RCV000623192.2 | |
Pathogenic (1) |
no assertion criteria provided
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Sep 28, 2018 | RCV001265442.1 |
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
(Oct 04, 2019)
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criteria provided, single submitter
Method: clinical testing
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Intellectual disability, autosomal dominant 40
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
de novo
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Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München
Accession: SCV001149706.1
First in ClinVar: Feb 03, 2020 Last updated: Feb 03, 2020 |
Sex: male
Tissue: blood
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Pathogenic
(Dec 07, 2022)
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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: SCV000710051.3
First in ClinVar: Apr 02, 2018 Last updated: Dec 17, 2022 |
Comment:
Nonsense variant in the C-terminus predicted to result in protein truncation, as the last 316 amino acids are lost, and other loss-of-function variants have been … (more)
Nonsense variant in the C-terminus predicted to result in protein truncation, as the last 316 amino acids are lost, and other loss-of-function variants have been reported downstream in the Human Gene Mutation Database (HGMD); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 28135719, 26751395, 25533962, 28191890, 34021018, 27535533, 24077912, 31785789, 33176815, 31278258) (less)
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Pathogenic
(Apr 26, 2017)
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criteria provided, single submitter
Method: clinical testing
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Inborn genetic diseases
Affected status: yes
Allele origin:
germline
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Ambry Genetics
Accession: SCV000742457.3
First in ClinVar: Apr 15, 2018 Last updated: Jan 07, 2023 |
Number of individuals with the variant: 1
Clinical Features:
Cortical dysplasia (present) , Global developmental delay (present) , Muscular hypotonia (present) , Hypertonia (present) , Hyperreflexia (present) , Tented upper lip vermilion (present) , … (more)
Cortical dysplasia (present) , Global developmental delay (present) , Muscular hypotonia (present) , Hypertonia (present) , Hyperreflexia (present) , Tented upper lip vermilion (present) , Cortical visual impairment (present) , Hypermetropia (present) , Exaggerated startle response (present) , Constipation (present) , Alternating esotropia (present) , Seborrheic dermatitis (present) , Hemangioma (present) , Tongue tie (present) , Feeding difficulties (present) , Recurrent upper respiratory tract infections (present) (less)
Sex: female
Ethnicity/Population group: Caucasian/Hispanic
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Pathogenic
(Mar 08, 2023)
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criteria provided, single submitter
Method: clinical testing
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Intellectual disability, autosomal dominant 40
Affected status: yes
Allele origin:
germline
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Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen
Accession: SCV003837561.1
First in ClinVar: Mar 11, 2023 Last updated: Mar 11, 2023 |
Clinical Features:
Hyperopic astigmatism (present) , Strabismus (present) , Cerebellar ataxia (present) , Reduced tendon reflexes (present) , Moderate global developmental delay (present)
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Pathogenic
(Mar 12, 2015)
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no assertion criteria provided
Method: literature only
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MENTAL RETARDATION, AUTOSOMAL DOMINANT 40
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000246266.1
First in ClinVar: Oct 05, 2015 Last updated: Oct 05, 2015 |
Comment on evidence:
In a girl with autosomal dominant mental retardation-40 (MRD40; 616579), the Deciphering Developmental Disorders Study (2015) identified a de novo heterozygous c.1489C-T transition in the … (more)
In a girl with autosomal dominant mental retardation-40 (MRD40; 616579), the Deciphering Developmental Disorders Study (2015) identified a de novo heterozygous c.1489C-T transition in the CHAMP1 gene, resulting in an arg497-to-ter (R497X) substitution. Functional studies of the variant were not performed. (less)
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Pathogenic
(Sep 28, 2018)
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no assertion criteria provided
Method: provider interpretation
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CHAMP1-related syndrome
Affected status: yes
Allele origin:
de novo
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GenomeConnect - Simons Searchlight
Accession: SCV001443573.1
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 2018-09-28 and interpreted as Pathogenic. The reporting laboratory … (more)
Submission from Simons Searchlight facilitated by GenomeConnect. Variant interpreted by the Simons Searchlight team most recently on 2018-09-28 and interpreted as Pathogenic. The reporting laboratory might also submit to ClinVar. This variant was identified in multiple probands enrolled in Simons Searchlight. (less)
Observation 1:
Number of individuals with the variant: 1
Clinical Features:
Caesarian section (present) , Abnormality of vision (present) , Hypermetropia (present) , Generalized hypotonia (present) , Otitis media (present)
Age: 0-9 years
Sex: female
Testing laboratory: Ambry Genetics
Date variant was reported to submitter: 2017-05-11
Testing laboratory interpretation: Pathogenic
Observation 2:
Number of individuals with the variant: 1
Clinical Features:
Autistic behavior (present) , Caesarian section (present) , Hyperbilirubinemia (present) , Neonatal hypotonia (present) , Abnormality of vision (present) , Amblyopia (present) , Generalized hypotonia … (more)
Autistic behavior (present) , Caesarian section (present) , Hyperbilirubinemia (present) , Neonatal hypotonia (present) , Abnormality of vision (present) , Amblyopia (present) , Generalized hypotonia (present) , Seizures (present) , Constipation (present) , Otitis media (present) , Pneumonia (present) , Leukemia (present) , Abnormality of the skeletal system (present) , High palate (present) , Abnormality of the skin (present) , Psoriasis (present) , Abnormality of the cardiovascular system (present) , Abnormality of the dentition (present) , Abnormality of pain sensation (present) (less)
Age: 10-19 years
Sex: male
Testing laboratory: Blueprint Genetics
Date variant was reported to submitter: 2017-09-08
Testing laboratory interpretation: Pathogenic
Observation 3:
Number of individuals with the variant: 1
Clinical Features:
Autistic behavior (present) , Abnormality of vision (present) , Hypermetropia (present) , Generalized hypotonia (present) , Gastroesophageal reflux (present) , Diarrhea (present) , Constipation (present) … (more)
Autistic behavior (present) , Abnormality of vision (present) , Hypermetropia (present) , Generalized hypotonia (present) , Gastroesophageal reflux (present) , Diarrhea (present) , Constipation (present) , Pneumonia (present) , Allergy (present) , Drug allergy (present) (less)
Age: 10-19 years
Sex: female
Testing laboratory: All Wales Genetics Laboratory,Institute of Medical Genetics
Date variant was reported to submitter: 2014-08-14
Testing laboratory interpretation: Pathogenic
Observation 4:
Number of individuals with the variant: 1
Clinical Features:
Neonatal respiratory distress (present) , Feeding difficulties in infancy (present) , Nystagmus (present) , Strabismus (present) , Clumsiness (present) , Generalized hypotonia (present) , Microcephaly … (more)
Neonatal respiratory distress (present) , Feeding difficulties in infancy (present) , Nystagmus (present) , Strabismus (present) , Clumsiness (present) , Generalized hypotonia (present) , Microcephaly (present) , Seizures (present) , Absence seizures (present) , Gastroesophageal reflux (present) , Constipation (present) , Otitis media (present) , Pneumonia (present) (less)
Age: 10-19 years
Sex: male
Testing laboratory: Centre de Génétique Moléculaire Hôpital Trousseau - Assistance Publique des Hôpitaux de Paris (APHP)
Date variant was reported to submitter: 2016-11-10
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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De novo pathogenic variants in CHAMP1 are associated with global developmental delay, intellectual disability, and dysmorphic facial features. | Tanaka AJ | Cold Spring Harbor molecular case studies | 2016 | PMID: 27148580 |
De Novo Truncating Mutations in the Kinetochore-Microtubules Attachment Gene CHAMP1 Cause Syndromic Intellectual Disability. | Isidor B | Human mutation | 2016 | PMID: 26751395 |
Large-scale discovery of novel genetic causes of developmental disorders. | Deciphering Developmental Disorders Study | Nature | 2015 | PMID: 25533962 |
CAMP (C13orf8, ZNF828) is a novel regulator of kinetochore-microtubule attachment. | Itoh G | The EMBO journal | 2011 | PMID: 21063390 |
Text-mined citations for rs782397980 ...
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.