VCV002674611.1 - ClinVar

NM_001375380.1(EBF3):c.1454_1455del (p.Thr485fs)

Germline

Classification

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.

(1)

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.

Likely pathogenic

criteria provided, single submitter

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_001375380.1(EBF3):c.1454_1455del (p.Thr485fs)

Variation ID: 2674611 Accession: VCV002674611.1

Type and length

Microsatellite, 2 bp

Location

Cytogenetic: 10q26.3 10: 129840950-129840951 (GRCh38) [ NCBI UCSC ] 10: 131639214-131639215 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	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	Dec 25, 2023	Dec 24, 2023	Apr 9, 2020

HGVS

Nucleotide	Protein	Molecular consequence
NM_001375380.1:c.1454_1455del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001362309.1:p.Thr485fs	frameshift
NM_001005463.3:c.1427_1428del	NP_001005463.1:p.Thr476fs	frameshift
NM_001005463.3:c.1427_1428delCA		frameshift
NM_001375379.1:c.1454_1455del	NP_001362308.1:p.Thr485fs	frameshift
NM_001375389.1:c.1454_1455del	NP_001362318.1:p.Thr485fs	frameshift
NM_001375390.1:c.1427_1428del	NP_001362319.1:p.Thr476fs	frameshift
NM_001375391.1:c.1454_1455del	NP_001362320.1:p.Thr485fs	frameshift
NM_001375392.1:c.1346-509_1346-508del		intron variant
NC_000010.11:g.129840951GT[1]
NC_000010.10:g.131639215GT[1]
NG_030038.1:g.127875CA[1]

... more HGVS ... less HGVS

Protein change

T476fs, T485fs

Other names

Canonical SPDI

NC_000010.11:129840949:TGTGT:TGT

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The 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.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

VarSome

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
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help 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.
EBF3		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	241	342

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help 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.
Hypotonia, ataxia, and delayed development syndrome	Likely pathogenic (1)	criteria provided, single submitter	Apr 9, 2020	RCV003459152.1

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 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 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.
Likely pathogenic (Apr 09, 2020)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Hypotonia, ataxia, and delayed development syndrome (Autosomal dominant inheritance) Affected status: yes Allele origin: germline	Division Of Personalized Genomic Medicine, Columbia University Irving Medical Center Accession: SCV004190149.1 First in ClinVar: Dec 24, 2023 Last updated: Dec 24, 2023	Publications: PubMed (1) PubMed: 29162653 Comment: The c.1427_1428delCA (p.Thr476SerfsTer4) variant in the EBF3 gene is a heterozygous frameshift variant, resulting in a premature stop codon downstream. This variant localizes to coding … (more) The c.1427_1428delCA (p.Thr476SerfsTer4) variant in the EBF3 gene is a heterozygous frameshift variant, resulting in a premature stop codon downstream. This variant localizes to coding exon 14 of the gene (16 coding exons in total; NM_001005463.3). This variant is absent in the Genome Aggregation Database (gnomAD), indicating it is not a common benign variant in the populations represented in this database. To the best of our knowledge, this specific variant has not been described in the literature to be associated with disease. However, loss-of-function variants in EBF3 have been established to be disease causing (PMID: 29162653). A nearby variant (p.Thr464Profs*10) has been reported in an affected individual (PMID: 29162653). No loss-of-function variants downstream to this one have been reported in affected individuals. (less) Clinical Features: Intellectual disability (present) , Microcephaly (present) , Failure to thrive (present) , Seizure (present) , Dysphagia (present) , Exotropia (present) , Motor delay (present) Age: 10-19 years Sex: female Ethnicity/Population group: African American

Comment:

The c.1427_1428delCA (p.Thr476SerfsTer4) variant in the EBF3 gene is a heterozygous frameshift variant, resulting in a premature stop codon downstream. This variant localizes to coding exon 14 of the gene (16 coding exons in total; NM_001005463.3). This variant is absent in the Genome Aggregation Database (gnomAD), indicating it is not a common benign variant in the populations represented in this database. To the best of our knowledge, this specific variant has not been described in the literature to be associated with disease. However, loss-of-function variants in EBF3 have been established to be disease causing (PMID: 29162653). A nearby variant (p.Thr464Profs*10) has been reported in an affected individual (PMID: 29162653). No loss-of-function variants downstream to this one have been reported in affected individuals.

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.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
De novo variants in EBF3 are associated with hypotonia, developmental delay, intellectual disability, and autism.	Tanaka AJ	Cold Spring Harbor molecular case studies	2017	PMID: 29162653

Text-mined citations for this variant ...

Record last updated Jul 15, 2024

ClinVar Genomic variation as it relates to human health

NM_001375380.1(EBF3):c.1454_1455del (p.Thr485fs)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...