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NM_001375380.1(EBF3):c.488G>A (p.Arg163Gln) AND Isolated Pierre-Robin syndrome

Germline classification:
Pathogenic (1 submission)
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
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:
RCV000663416.3

Allele description [Variation Report for NM_001375380.1(EBF3):c.488G>A (p.Arg163Gln)]

NM_001375380.1(EBF3):c.488G>A (p.Arg163Gln)

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.488G>A (p.Arg163Gln)
HGVS:
  • NC_000010.11:g.129957324C>T
  • NG_030038.1:g.11504G>A
  • NM_001005463.3:c.488G>A
  • NM_001375379.1:c.488G>A
  • NM_001375380.1:c.488G>AMANE SELECT
  • NM_001375389.1:c.488G>A
  • NM_001375390.1:c.488G>A
  • NM_001375391.1:c.488G>A
  • NM_001375392.1:c.488G>A
  • NP_001005463.1:p.Arg163Gln
  • NP_001362308.1:p.Arg163Gln
  • NP_001362309.1:p.Arg163Gln
  • NP_001362318.1:p.Arg163Gln
  • NP_001362319.1:p.Arg163Gln
  • NP_001362320.1:p.Arg163Gln
  • NP_001362321.1:p.Arg163Gln
  • NC_000010.10:g.131755588C>T
  • NM_001005463.2:c.488G>A
  • p.R163Q
Protein change:
R163Q; ARG163GLN
Links:
OMIM: 607407.0005; dbSNP: rs1057519389
NCBI 1000 Genomes Browser:
rs1057519389
Molecular consequence:
  • NM_001005463.3:c.488G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375379.1:c.488G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375380.1:c.488G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375389.1:c.488G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375390.1:c.488G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375391.1:c.488G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375392.1:c.488G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Isolated Pierre-Robin syndrome
Synonyms:
Pierre Robin's sequence; Glossoptosis, micrognathia, and cleft palate; Pierre Robin Syndrome; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0009869; MedGen: C0031900; Orphanet: 718; OMIM: 261800; Human Phenotype Ontology: HP:0000201

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000786711Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard - Broad Institute Center for Mendelian Genomics (CMG)
criteria provided, single submitter

(ACMG Guidelines, 2015)		Pathogenicgermlineresearch

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
Unspecifiedgermlineyes11not providednot providednot providedresearch

Citations

PubMed

A Syndromic Neurodevelopmental Disorder Caused by De Novo Variants in EBF3.

Chao HT, Davids M, Burke E, Pappas JG, Rosenfeld JA, McCarty AJ, Davis T, Wolfe L, Toro C, Tifft C, Xia F, Stong N, Johnson TK, Warr CG; Undiagnosed Diseases Network., Yamamoto S, Adams DR, Markello TC, Gahl WA, Bellen HJ, Wangler MF, Malicdan MCV.

Am J Hum Genet. 2017 Jan 5;100(1):128-137. doi: 10.1016/j.ajhg.2016.11.018. Epub 2016 Dec 22.

PubMed [citation]
PMID:
28017372
PMCID:
PMC5223093

De Novo Mutations in EBF3 Cause a Neurodevelopmental Syndrome.

Sleven H, Welsh SJ, Yu J, Churchill MEA, Wright CF, Henderson A, Horvath R, Rankin J, Vogt J, Magee A, McConnell V, Green A, King MD, Cox H, Armstrong L, Lehman A, Nelson TN; Deciphering Developmental Disorders study.; CAUSES study., Williams J, Clouston P, Hagman J, et al.

Am J Hum Genet. 2017 Jan 5;100(1):138-150. doi: 10.1016/j.ajhg.2016.11.020. Epub 2016 Dec 23.

PubMed [citation]
PMID:
28017370
PMCID:
PMC5223060
See all PubMed Citations (3)

Details of each submission

From Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard - Broad Institute Center for Mendelian Genomics (CMG), SCV000786711.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1Unspecified1not providednot providedresearch PubMed (3)

Description

The heterozygous p.Arg163Gln variant was identified by our study in one individual with Robin sequence and severe hypotonia with abnormal brain MRI findings. Trio analysis showed this variant occurred de novo. The p.Arg163Gln variant is located in the transcription factor EBF3 and occurs adjacent to a (de novo) ClinVar pathogenic variant for HADDS. The arginine (and adjacent serine) is highly conserved at the amino acid level and the nucleotide position is also highly conserved. The variant occurs in the conserved DNA binding and dimerization (homodimer) domains. Additionally, the c.488G>A variant occurs 2 nucleotides from the splice acceptor site of intron 5 so the missense variants in this region could potentially be functioning in a LoF mechanism and which may lead to slightly more mild phenotypes than the dominant negative acting missense variants in this gene. Additionally, of the first 3 initial papers describing this disorder, two patients had a G>A at the same position (PMID: 28017372) while another patient had a G>C at the same nucleotide position resulting in a p.Arg163Pro (PMID: 28017370). In summary, taken together, the evidence available suggest this variant is pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot provided1not provided1not provided

Last Updated: Mar 30, 2024