ClinVar Genomic variation as it relates to human health
NM_000390.4(CHM):c.877C>T (p.Arg293Ter)
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_000390.4(CHM):c.877C>T (p.Arg293Ter)
Variation ID: 11154 Accession: VCV000011154.32
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: Xq21.2 X: 85957918 (GRCh38) [ NCBI UCSC ] X: 85212923 (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 15, 2017 Mar 10, 2024 Jul 24, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000390.4:c.877C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000381.1:p.Arg293Ter nonsense NM_001320959.1:c.433C>T NP_001307888.1:p.Arg145Ter nonsense NM_001362517.1:c.433C>T NP_001349446.1:p.Arg145Ter nonsense NM_001362518.2:c.433C>T NP_001349447.1:p.Arg145Ter nonsense NM_001362519.1:c.433C>T NP_001349448.1:p.Arg145Ter nonsense NC_000023.11:g.85957918G>A NC_000023.10:g.85212923G>A NG_009874.2:g.94645C>T LRG_699:g.94645C>T LRG_699t1:c.877C>T LRG_699p1:p.Arg293* - Protein change
- R293*, R145*
- Other names
- R294*
- NP_000381.1:p.(Arg293Ter)
- Canonical SPDI
- NC_000023.11:85957917: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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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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CHM | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
782 | 1014 |
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 (4) |
criteria provided, single submitter
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Jul 24, 2023 | RCV000011904.11 | |
Pathogenic (4) |
criteria provided, multiple submitters, no conflicts
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Mar 13, 2023 | RCV000078687.28 |
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
(Dec 12, 2017)
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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: SCV000680505.1
First in ClinVar: Feb 13, 2018 Last updated: Feb 13, 2018 |
Comment:
The R293X variant in the CHM gene has been reported previously (also as R294X due to alternate nomenclature) in multiple unrelated patients with choroideremia (van … (more)
The R293X variant in the CHM gene has been reported previously (also as R294X due to alternate nomenclature) in multiple unrelated patients with choroideremia (van Bokhoven et al., 1994; Jolly et al., 2015; McLaren et al., 2015; Sanchez-Alcudia et al., 2016). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The R293X variant is not observed in large population cohorts (Lek et al., 2016). We interpret R293X as a pathogenic variant. (less)
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Pathogenic
(Oct 29, 2013)
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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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Eurofins Ntd Llc (ga)
Accession: SCV000110547.8
First in ClinVar: Jan 17, 2014 Last updated: Feb 13, 2018 |
Number of individuals with the variant: 1
Sex: mixed
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Pathogenic
(Aug 01, 2017)
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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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CeGaT Center for Human Genetics Tuebingen
Accession: SCV001248391.19
First in ClinVar: May 09, 2020 Last updated: Mar 10, 2024 |
Number of individuals with the variant: 1
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Pathogenic
(Jul 24, 2023)
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criteria provided, single submitter
Method: research
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Choroideremia
Affected status: yes
Allele origin:
germline
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Ophthalmic Genetics Group, Institute of Molecular and Clinical Ophthalmology Basel
Accession: SCV004030378.1
First in ClinVar: Sep 03, 2023 Last updated: Sep 03, 2023 |
Comment:
Clinical significance based on ACMG v2.0
Number of individuals with the variant: 1
Sex: male
Geographic origin: Portugal
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Pathogenic
(Mar 13, 2023)
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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: SCV001377144.5
First in ClinVar: Jul 16, 2020 Last updated: Feb 14, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 11154). This premature translational stop signal … (more)
For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 11154). This premature translational stop signal has been observed in individual(s) with choroidemia (PMID: 26133251, 28559085). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg293*) in the CHM gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CHM are known to be pathogenic (PMID: 9067750, 23811034). (less)
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Pathogenic
(Jul 01, 1994)
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no assertion criteria provided
Method: literature only
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CHOROIDEREMIA
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000032137.2
First in ClinVar: Apr 04, 2013 Last updated: Jun 15, 2017 |
Comment on evidence:
In a mutation screening of patients from 15 Danish and Swedish families with choroideremia (CHM; 303100), van Bokhoven et al. (1994) found mainly deletions or … (more)
In a mutation screening of patients from 15 Danish and Swedish families with choroideremia (CHM; 303100), van Bokhoven et al. (1994) found mainly deletions or insertions. There were, however, 4 single nucleotide substitutions of which 2 were missense mutations and 2 were splice errors. One of the missense mutations (in patient LN) was a C-to-T transition at nucleotide 907 resulting in a change of arg294 to a termination codon. (less)
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Pathogenic
(Jun 23, 2019)
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no assertion criteria provided
Method: research
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Choroideremia
Affected status: yes
Allele origin:
inherited
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Sharon lab, Hadassah-Hebrew University Medical Center
Accession: SCV001160981.1
First in ClinVar: Feb 16, 2020 Last updated: Feb 16, 2020 |
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not provided
(-)
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no classification provided
Method: literature only
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Choroideremia
Affected status: unknown
Allele origin:
germline
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GeneReviews
Accession: SCV002012455.2
First in ClinVar: Nov 13, 2021 Last updated: Oct 01, 2022 |
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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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The first genetic landscape of inherited retinal dystrophies in Portuguese patients identifies recurrent homozygous mutations as a frequent cause of pathogenesis. | Peter VG | PNAS nexus | 2023 | PMID: 36909829 |
Clinically Focused Molecular Investigation of 1000 Consecutive Families with Inherited Retinal Disease. | Stone EM | Ophthalmology | 2017 | PMID: 28559085 |
Functional Defects in Color Vision in Patients With Choroideremia. | Jolly JK | American journal of ophthalmology | 2015 | PMID: 26133251 |
A clinical molecular genetic service for United Kingdom families with choroideraemia. | Ramsden SC | European journal of medical genetics | 2013 | PMID: 23811034 |
Comprehensive mutation analysis (20 families) of the choroideremia gene reveals a missense variant that prevents the binding of REP1 with Rab geranylgeranyl transferase. | Esposito G | Human mutation | 2011 | PMID: 21905166 |
Novel types of mutation in the choroideremia ( CHM) gene: a full-length L1 insertion and an intronic mutation activating a cryptic exon. | van den Hurk JA | Human genetics | 2003 | PMID: 12827496 |
Molecular basis of choroideremia (CHM): mutations involving the Rab escort protein-1 (REP-1) gene. | van den Hurk JA | Human mutation | 1997 | PMID: 9067750 |
Cloning and characterization of the human choroideremia gene. | van Bokhoven H | Human molecular genetics | 1994 | PMID: 7981670 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=CHM | - | - | - | - |
Text-mined citations for rs132630266 ...
HelpRecord last updated Mar 11, 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.