10-129840398-GGAGGGTGACCGAA-G

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2

The NM_001375380.1(EBF3):​c.1593_1605delTTCGGTCACCCTC​(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

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.89
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]

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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 rank MANE Protein UniProt
EBF3NM_001375380.1 linkc.1593_1605delTTCGGTCACCCTC p.Ser532LeufsTer22 frameshift_variant Exon 15 of 17 ENST00000440978.2 NP_001362309.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
EBF3ENST00000440978.2 linkc.1593_1605delTTCGGTCACCCTC p.Ser532LeufsTer22 frameshift_variant Exon 15 of 17 3 NM_001375380.1 ENSP00000387543.2 H0Y3W9
EBF3ENST00000368648.8 linkc.1535-77_1535-65delTTCGGTCACCCTC intron_variant Intron 15 of 16 1 ENSP00000357637.3 Q9H4W6-2
EBF3ENST00000355311.10 linkc.1593_1605delTTCGGTCACCCTC p.Ser532LeufsTer22 frameshift_variant Exon 15 of 16 5 ENSP00000347463.4 Q9H4W6-1
EBF3ENST00000675373.1 linkn.1207-77_1207-65delTTCGGTCACCCTC intron_variant Intron 11 of 13

Frequencies

GnomAD3 genomes
Cov.:
33
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
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
Aug 08, 2022
Department of Genetics, Rouen University Hospital, Normandy Center for Genomic and Personalized Medicine
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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: chr10-131638662; API