10-129840307-AC-A

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate

The NM_001375380.1(EBF3):​c.1696del​(p.Val566TrpfsTer30) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 33)

Consequence

EBF3
NM_001375380.1 frameshift

Scores

Not classified

Clinical Significance

Pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 7.82
Variant links:
Genes affected
EBF3 (HGNC:19087): (EBF transcription factor 3) This gene encodes a member of the early B-cell factor (EBF) family of DNA binding transcription factors. EBF proteins are involved in B-cell differentiation, bone development and neurogenesis, and may also function as tumor suppressors. The encoded protein inhibits cell survival through the regulation of genes involved in cell cycle arrest and apoptosis, and aberrant methylation or deletion of this gene may play a role in multiple malignancies including glioblastoma multiforme and gastric carcinoma. [provided by RefSeq, Sep 2011]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 12 ACMG points.

PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 10-129840307-AC-A is Pathogenic according to our data. Variant chr10-129840307-AC-A is described in ClinVar as [Pathogenic]. Clinvar id is 1068622.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
EBF3NM_001375380.1 linkuse as main transcriptc.1696del p.Val566TrpfsTer30 frameshift_variant 15/17 ENST00000440978.2 NP_001362309.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
EBF3ENST00000440978.2 linkuse as main transcriptc.1696del p.Val566TrpfsTer30 frameshift_variant 15/173 NM_001375380.1 ENSP00000387543
EBF3ENST00000368648.8 linkuse as main transcriptc.1561del p.Val521TrpfsTer27 frameshift_variant 16/171 ENSP00000357637 A1Q9H4W6-2
EBF3ENST00000355311.10 linkuse as main transcriptc.1696del p.Val566TrpfsTer27 frameshift_variant 15/165 ENSP00000347463 P4Q9H4W6-1
EBF3ENST00000675373.1 linkuse as main transcriptn.1233del non_coding_transcript_exon_variant 12/14

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
37
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Pathogenic:1
Pathogenic, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpDec 06, 2017This sequence change creates a premature translational stop signal (p.Val521Trpfs*27) in the EBF3 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with EBF3-related disease. Loss-of-function variants in EBF3 are known to be pathogenic (PMID: 28017370, 28017373). For these reasons, this variant has been classified as Pathogenic. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-131638571; API