10-129840398-GGAGGGTGACCGAA-G
Position:
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2
The NM_001375380.1(EBF3):c.1593_1605del(p.Ser532LeufsTer22) 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 Uncertain significance (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 33)
Consequence
EBF3
NM_001375380.1 frameshift
NM_001375380.1 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 9.89
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]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 10 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;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
EBF3 | NM_001375380.1 | c.1593_1605del | p.Ser532LeufsTer22 | frameshift_variant | 15/17 | ENST00000440978.2 | NP_001362309.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
EBF3 | ENST00000440978.2 | c.1593_1605del | p.Ser532LeufsTer22 | frameshift_variant | 15/17 | 3 | NM_001375380.1 | ENSP00000387543 | ||
EBF3 | ENST00000368648.8 | c.1535-77_1535-65del | intron_variant | 1 | ENSP00000357637 | A1 | ||||
EBF3 | ENST00000355311.10 | c.1593_1605del | p.Ser532LeufsTer22 | frameshift_variant | 15/16 | 5 | ENSP00000347463 | P4 | ||
EBF3 | ENST00000675373.1 | n.1207-77_1207-65del | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome Cov.: 33
GnomAD4 genome
Cov.:
33
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Autism spectrum disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Department of Genetics, Rouen University Hospital, Normandy Center for Genomic and Personalized Medicine | Aug 08, 2022 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.