NM_001375380.1(EBF3):c.196A>G (p.Asn66Asp) AND Hypotonia, ataxia, and delayed development syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 7, 2017
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000416941.1

Allele description [Variation Report for NM_001375380.1(EBF3):c.196A>G (p.Asn66Asp)]

NM_001375380.1(EBF3):c.196A>G (p.Asn66Asp)

Gene:

EBF3:EBF transcription factor 3 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

10q26.3

Genomic location:

Preferred name:

NM_001375380.1(EBF3):c.196A>G (p.Asn66Asp)

HGVS:

NC_000010.11:g.129963462T>C
NG_030038.1:g.5366A>G
NM_001005463.3:c.196A>G
NM_001375379.1:c.196A>G
NM_001375380.1:c.196A>GMANE SELECT
NM_001375389.1:c.196A>G
NM_001375390.1:c.196A>G
NM_001375391.1:c.196A>G
NM_001375392.1:c.196A>G
NP_001005463.1:p.Asn66Asp
NP_001362308.1:p.Asn66Asp
NP_001362309.1:p.Asn66Asp
NP_001362318.1:p.Asn66Asp
NP_001362319.1:p.Asn66Asp
NP_001362320.1:p.Asn66Asp
NP_001362321.1:p.Asn66Asp
NC_000010.10:g.131761726T>C
NM_001005463.2:c.196A>G

Protein change:

N66D; ASN66ASP

Links:

OMIM: 607407.0002; dbSNP: rs1057519518

NCBI 1000 Genomes Browser:

rs1057519518

Molecular consequence:

NM_001005463.3:c.196A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001375379.1:c.196A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001375380.1:c.196A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001375389.1:c.196A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001375390.1:c.196A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001375391.1:c.196A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001375392.1:c.196A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hypotonia, ataxia, and delayed development syndrome (HADDS)
Identifiers:: MONDO: MONDO:0015021; MedGen: C4310618; OMIM: 617330

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000494484	OMIM	no assertion criteria provided	Pathogenic (Feb 7, 2017)	germline	literature only	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000494484

OMIM

no assertion criteria provided

Pathogenic
(Feb 7, 2017)

germline

literature only

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Mutations in EBF3 Disturb Transcriptional Profiles and Cause Intellectual Disability, Ataxia, and Facial Dysmorphism.

Harms FL, Girisha KM, Hardigan AA, Kortüm F, Shukla A, Alawi M, Dalal A, Brady L, Tarnopolsky M, Bird LM, Ceulemans S, Bebin M, Bowling KM, Hiatt SM, Lose EJ, Primiano M, Chung WK, Juusola J, Akdemir ZC, Bainbridge M, Charng WL, Drummond-Borg M, et al.

Am J Hum Genet. 2017 Jan 5;100(1):117-127. doi: 10.1016/j.ajhg.2016.11.012. Epub 2016 Dec 22.

PubMed [citation]

PMID:: 28017373
PMCID:: PMC5223027

Details of each submission

From OMIM, SCV000494484.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In a 16.5-year-old boy (subject 4) with hypotonia, ataxia, and delayed development syndrome (HADDS; 617330), Harms et al. (2017) reported a de novo heterozygous c.196A-G transition (c.196A-G, NM_001005463.2) in exon 2 of the EBF3 gene, resulting in an asn66-to-asp (N66D) substitution at a highly conserved residue in the DNA-binding domain. The authors stated that the variant was found by whole-exome sequencing by groups that independently submitted to GeneMatcher. The mutation was not found in the 1000 Genomes Project, Exome Variant Server, or ExAC databases. In vitro functional expression studies in HEK293 cells showed that the mutant protein localized to the nucleus but with additional altered localization in the cytoplasm, decreased association with chromatin, and significantly decreased ability to activate transcription of a reporter gene compared to controls. Transcriptional activation was also reduced when the mutation was coexpressed with the wildtype gene, supporting a possible dominant-negative effect.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jul 15, 2024

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