ClinVar Genomic variation as it relates to human health
NM_001375380.1(EBF3):c.487C>T (p.Arg163Trp)
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.
Pathogenic(1); Uncertain significance(1)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_001375380.1(EBF3):c.487C>T (p.Arg163Trp)
Variation ID: 374797 Accession: VCV000374797.10
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 10q26.3 10: 129957325 (GRCh38) [ NCBI UCSC ] 10: 131755589 (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 Jul 7, 2018 Oct 1, 2022 Sep 23, 2021 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001375380.1:c.487C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001362309.1:p.Arg163Trp missense NM_001005463.3:c.487C>T NP_001005463.1:p.Arg163Trp missense NM_001375379.1:c.487C>T NP_001362308.1:p.Arg163Trp missense NM_001375389.1:c.487C>T NP_001362318.1:p.Arg163Trp missense NM_001375390.1:c.487C>T NP_001362319.1:p.Arg163Trp missense NM_001375391.1:c.487C>T NP_001362320.1:p.Arg163Trp missense NM_001375392.1:c.487C>T NP_001362321.1:p.Arg163Trp missense NC_000010.11:g.129957325G>A NC_000010.10:g.131755589G>A NG_030038.1:g.11503C>T - Protein change
- R163W
- Other names
- p.Arg163Trp
- Canonical SPDI
- NC_000010.11:129957324:G:A
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- variation affecting protein function Variation Ontology [VariO:0003]
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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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EBF3 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
215 | 316 |
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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Conflicting interpretations of pathogenicity (4) |
criteria provided, conflicting classifications
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Sep 23, 2021 | RCV000415489.12 |
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
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
Help
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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Uncertain significance
(Nov 28, 2016)
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criteria provided, single submitter
Method: clinical testing
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Hypotonia, ataxia, and delayed development syndrome
Affected status: unknown
Allele origin:
de novo
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Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV000493129.2
First in ClinVar: Jan 20, 2017 Last updated: Jul 07, 2018 |
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Pathogenic
(Sep 23, 2021)
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criteria provided, single submitter
Method: clinical testing
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Hypotonia, ataxia, and delayed development syndrome
Affected status: yes
Allele origin:
de novo
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Molecular Diagnostics Laboratory, M Health Fairview: University of Minnesota
Accession: SCV001981525.1
First in ClinVar: Oct 21, 2021 Last updated: Oct 21, 2021 |
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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Hypotonia, ataxia, and delayed development syndrome
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
de novo
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Sezerman Lab, Dept of Biostatistics and Bioinformatics, Acibadem Mehmet Ali Aydinlar University
Accession: SCV001573769.1
First in ClinVar: May 10, 2021 Last updated: May 10, 2021 |
Comment:
The variant R163W was reported in a girl by Blackburn et. al. They also showed the impact of the variant on protein structure. Their findings … (more)
The variant R163W was reported in a girl by Blackburn et. al. They also showed the impact of the variant on protein structure. Their findings demonstrated that p.R163W could cause decreased DNA binding affinity and differential transcriptional activation. In summary, R163W is classified as pathogenic based on the previous studies and our segregation study that shows the absence of the variant in the biological parents of the proband. (less)
Clinical Features:
Generalized hypotonia (present) , Global developmental delay (present) , Low-set ears (present) , Pain insensitivity (present) , Strabismus (present)
Age: 0-9 years
Sex: male
Ethnicity/Population group: Turkish
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not provided
(-)
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no classification provided
Method: literature only
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Hypotonia, ataxia, and delayed development syndrome
Affected status: unknown
Allele origin:
germline
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GeneReviews
Accession: SCV001737493.2
First in ClinVar: Jun 19, 2021 Last updated: Oct 01, 2022 |
Comment:
Recurrent variants affecting codon 163 are located in a CpG island, a mutational hotspot
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Germline Functional Evidence
Functional
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The functional consequence of the variant, based on experimental evidence and provided by the submitter. consequence |
Method
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A brief description of the method used to determine the functional consequence of the variant. A citation for the method is included, when provided by the submitter. |
Result
Help
A brief description of the result of this method for 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
Help
This column includes more information supporting functional evidence for the germline classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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variation affecting protein function
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Sezerman Lab, Dept of Biostatistics and Bioinformatics, Acibadem Mehmet Ali Aydinlar University
Accession: SCV001573769.1
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Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Novel de novo variant in EBF3 is likely to impact DNA binding in a patient with a neurodevelopmental disorder and expanded phenotypes: patient report, in silico functional assessment, and review of published cases. | Blackburn PR | Cold Spring Harbor molecular case studies | 2017 | DOI: 10.1101/mcs.a001743 |
Novel de novo variant in EBF3 is likely to impact DNA binding in a patient with a neurodevelopmental disorder and expanded phenotypes: patient report, in silico functional assessment, and review of published cases. | Blackburn PR | Cold Spring Harbor molecular case studies | 2017 | PMID: 28487885 |
Text-mined citations for rs1057519092 ...
HelpRecord last updated Feb 04, 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.