ClinVar Genomic variation as it relates to human health
NM_001005273.3(CHD3):c.3515G>A (p.Arg1172Gln)
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_001005273.3(CHD3):c.3515G>A (p.Arg1172Gln)
Variation ID: 549743 Accession: VCV000549743.16
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17p13.1 17: 7903291 (GRCh38) [ NCBI UCSC ] 17: 7806609 (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 Nov 3, 2018 May 20, 2023 Sep 2, 2021 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001005273.3:c.3515G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001005273.1:p.Arg1172Gln missense NM_001005271.3:c.3692G>A NP_001005271.2:p.Arg1231Gln missense NM_005852.4:c.3515G>A NP_005843.2:p.Arg1172Gln missense NC_000017.11:g.7903291G>A NC_000017.10:g.7806609G>A - Protein change
- R1172Q, R1231Q
- Other names
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- Canonical SPDI
- NC_000017.11:7903290: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
Help
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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CHD3 | - | - |
GRCh38 GRCh37 |
381 | 460 |
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
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. |
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Likely pathogenic (1) |
no assertion criteria provided
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May 3, 2018 | RCV000714499.2 | |
Pathogenic/Likely pathogenic (7) |
criteria provided, multiple submitters, no conflicts
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Jul 26, 2021 | RCV000722155.17 | |
Pathogenic (1) |
criteria provided, single submitter
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Sep 2, 2021 | RCV001855425.4 |
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
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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
(Feb 19, 2019)
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criteria provided, single submitter
Method: curation
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Snijders Blok-Campeau syndrome
Affected status: unknown
Allele origin:
unknown
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SIB Swiss Institute of Bioinformatics
Accession: SCV000930104.1
First in ClinVar: Aug 05, 2019 Last updated: Aug 05, 2019 |
Comment:
This variant is interpreted as a Pathogenic for Snijders Blok-Campeau syndrome, autosomal dominant. The following ACMG Tag(s) were applied: PM2 : Absent from controls (or … (more)
This variant is interpreted as a Pathogenic for Snijders Blok-Campeau syndrome, autosomal dominant. The following ACMG Tag(s) were applied: PM2 : Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. PM6-Strong : Multiple de novo occurrences, but without confirmation of paternity and maternity (PMID:30397230). PM1-supporting : PM1 downgraded in strength to Supporting. PP2 : Missense variant in a gene that has a low rate of benign missense variation and in which missense variants are a common mechanism of disease. PP3 : Multiple lines of computational evidence support a deleterious effect on the gene or gene product. PS3 : Well-established functional studies show a deleterious effect (PMID:30397230). (less)
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Pathogenic
(Feb 24, 2020)
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criteria provided, single submitter
Method: clinical testing
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Snijders Blok-Campeau syndrome
(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: SCV001430069.1
First in ClinVar: Aug 21, 2020 Last updated: Aug 21, 2020 |
Clinical Features:
Intellectual disability, mild (present) , Delayed speech and language development (present) , Abnormal aggressive, impulsive or violent behavior (present)
Sex: male
Tissue: blood
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Pathogenic
(Oct 08, 2019)
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criteria provided, single submitter
Method: clinical testing
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Snijders Blok-Campeau syndrome
Affected status: yes
Allele origin:
de novo
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Baylor Genetics
Accession: SCV001521687.1
First in ClinVar: Mar 22, 2021 Last updated: Mar 22, 2021 |
Comment:
This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868].
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Pathogenic
(Jul 26, 2021)
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criteria provided, single submitter
Method: clinical testing
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Snijders Blok-Campeau syndrome
Affected status: yes
Allele origin:
unknown
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Institute of Human Genetics, University of Leipzig Medical Center
Accession: SCV001428663.2
First in ClinVar: Aug 17, 2020 Last updated: Oct 02, 2021 |
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Likely pathogenic
(Jun 17, 2021)
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criteria provided, single submitter
Method: clinical testing
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Snijders Blok-Campeau syndrome
Affected status: yes
Allele origin:
unknown
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Department of Genetics, Rouen University Hospital, Normandy Center for Genomic and Personalized Medicine
Accession: SCV002102958.1
First in ClinVar: Mar 12, 2022 Last updated: Mar 12, 2022 |
Sex: female
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Pathogenic
(Sep 02, 2021)
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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: SCV002152880.1
First in ClinVar: Mar 28, 2022 Last updated: Mar 28, 2022 |
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Likely pathogenic
(May 03, 2018)
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no assertion criteria provided
Method: research
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Intellectual disability
Affected status: yes
Allele origin:
germline
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CHU Sainte-Justine Research Center, University of Montreal
Accession: SCV000787645.1
First in ClinVar: Nov 03, 2018 Last updated: Nov 03, 2018 |
Observation 1: Observation 2: Observation 3: |
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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Snijders Blok-Campeau syndrome
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
de novo
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Génétique des Maladies du Développement, Hospices Civils de Lyon
Accession: SCV002515963.1
First in ClinVar: May 24, 2022 Last updated: May 24, 2022 |
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Pathogenic
(May 12, 2023)
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no assertion criteria provided
Method: literature only
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SNIJDERS BLOK-CAMPEAU SYNDROME
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000854573.4
First in ClinVar: Dec 02, 2018 Last updated: May 20, 2023 |
Comment on evidence:
In 3 unrelated patients (patients 26, 27, and 28) with Snijders Blok-Campeau syndrome (SNIBCPS; 618205), Snijders Blok et al. (2018) identified a de novo heterozygous … (more)
In 3 unrelated patients (patients 26, 27, and 28) with Snijders Blok-Campeau syndrome (SNIBCPS; 618205), Snijders Blok et al. (2018) identified a de novo heterozygous c.3515G-A transition (c.3515G-A, NM_001005273.2) in the CHD3 gene, resulting in an arg1172-to-gln (R1172Q) substitution at a highly conserved residue in the helicase domain. The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, was not found in the gnomAD database. In vitro functional expression studies in HEK293 cells showed that the R1172Q mutation impaired ATP hydrolysis activity and impaired chromatin remodeling capacities as measured by restriction enzyme accessibility to nucleosomal DNA compared to wildtype. (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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CHD3 helicase domain mutations cause a neurodevelopmental syndrome with macrocephaly and impaired speech and language. | Snijders Blok L | Nature communications | 2018 | PMID: 30397230 |
Text-mined citations for rs1567861501 ...
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.