chr10-129840897-A-C
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2
The NM_001375380.1(EBF3):āc.1508T>Gā(p.Val503Gly) variant causes a missense 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 (ā ).
Frequency
Genomes: š 0.0000066 ( 0 hom., cov: 33)
Failed GnomAD Quality Control
Consequence
EBF3
NM_001375380.1 missense
NM_001375380.1 missense
Scores
5
10
4
Clinical Significance
Conservation
PhyloP100: 9.11
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 Uncertain_significance. Variant got 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), EBF3. . Gene score misZ 3.6113 (greater than the threshold 3.09). Trascript score misZ 3.1409 (greater than threshold 3.09). GenCC has associacion of gene with hypotonia, ataxia, and delayed development syndrome.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
EBF3 | NM_001375380.1 | c.1508T>G | p.Val503Gly | missense_variant | 14/17 | ENST00000440978.2 | NP_001362309.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
EBF3 | ENST00000440978.2 | c.1508T>G | p.Val503Gly | missense_variant | 14/17 | 3 | NM_001375380.1 | ENSP00000387543 | ||
EBF3 | ENST00000368648.8 | c.1481T>G | p.Val494Gly | missense_variant | 15/17 | 1 | ENSP00000357637 | A1 | ||
EBF3 | ENST00000355311.10 | c.1508T>G | p.Val503Gly | missense_variant | 14/16 | 5 | ENSP00000347463 | P4 | ||
EBF3 | ENST00000675373.1 | n.1153T>G | non_coding_transcript_exon_variant | 11/14 |
Frequencies
GnomAD3 genomes AF: 0.00 AC: 1AN: 151966Hom.: 0 Cov.: 33 FAILED QC
GnomAD3 genomes
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GnomAD4 exome Cov.: 32
GnomAD4 exome
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GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000658 AC: 1AN: 151966Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74190
GnomAD4 genome
Data not reliable, filtered out with message: AS_VQSR
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center | Mar 01, 2024 | PM2, PP2, PP3 - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
.;D
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
.;M
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D
REVEL
Uncertain
Sift
Pathogenic
D;D
Sift4G
Uncertain
T;T
Polyphen
P;.
Vest4
MutPred
Loss of stability (P = 0.007);.;
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at