10-129840949-CTG-C
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001375380.1(EBF3):c.1454_1455delCA(p.Thr485SerfsTer4) 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 Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001375380.1 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
EBF3 | NM_001375380.1 | c.1454_1455delCA | p.Thr485SerfsTer4 | frameshift_variant | Exon 14 of 17 | ENST00000440978.2 | NP_001362309.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
EBF3 | ENST00000440978.2 | c.1454_1455delCA | p.Thr485SerfsTer4 | frameshift_variant | Exon 14 of 17 | 3 | NM_001375380.1 | ENSP00000387543.2 | ||
EBF3 | ENST00000368648.8 | c.1427_1428delCA | p.Thr476SerfsTer4 | frameshift_variant | Exon 15 of 17 | 1 | ENSP00000357637.3 | |||
EBF3 | ENST00000355311.10 | c.1454_1455delCA | p.Thr485SerfsTer4 | frameshift_variant | Exon 14 of 16 | 5 | ENSP00000347463.4 | |||
EBF3 | ENST00000675373.1 | n.1099_1100delCA | non_coding_transcript_exon_variant | Exon 11 of 14 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Hypotonia, ataxia, and delayed development syndrome Pathogenic:1
The c.1427_1428delCA (p.Thr476SerfsTer4) variant in the EBF3 gene is a heterozygous frameshift variant, resulting in a premature stop codon downstream. This variant localizes to coding exon 14 of the gene (16 coding exons in total; NM_001005463.3). This variant is absent in the Genome Aggregation Database (gnomAD), indicating it is not a common benign variant in the populations represented in this database. To the best of our knowledge, this specific variant has not been described in the literature to be associated with disease. However, loss-of-function variants in EBF3 have been established to be disease causing (PMID: 29162653). A nearby variant (p.Thr464Profs*10) has been reported in an affected individual (PMID: 29162653). No loss-of-function variants downstream to this one have been reported in affected individuals. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.