10-129840963-GACTGCTGGGGAGT-G
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_001375380.1(EBF3):c.1429_1441delACTCCCCAGCAGT(p.Thr477ProfsTer10) 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
Consequence
NM_001375380.1 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
EBF3 | NM_001375380.1 | c.1429_1441delACTCCCCAGCAGT | p.Thr477ProfsTer10 | 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.1429_1441delACTCCCCAGCAGT | p.Thr477ProfsTer10 | frameshift_variant | Exon 14 of 17 | 3 | NM_001375380.1 | ENSP00000387543.2 | ||
EBF3 | ENST00000368648.8 | c.1402_1414delACTCCCCAGCAGT | p.Thr468ProfsTer10 | frameshift_variant | Exon 15 of 17 | 1 | ENSP00000357637.3 | |||
EBF3 | ENST00000355311.10 | c.1429_1441delACTCCCCAGCAGT | p.Thr477ProfsTer10 | frameshift_variant | Exon 14 of 16 | 5 | ENSP00000347463.4 | |||
EBF3 | ENST00000675373.1 | n.1074_1086delACTCCCCAGCAGT | non_coding_transcript_exon_variant | Exon 11 of 14 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Inborn genetic diseases Pathogenic:1
The c.1402_1414del13 (p.T468Pfs*10) alteration, located in exon 14 (coding exon 14) of the EBF3 gene, consists of a deletion of 13 nucleotides from position 1402 to 1414, causing a translational frameshift with a predicted alternate stop codon after 10 amino acids. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This variant has been determined to be the result of a de novo mutation in one individual with features consistent with EBF3-related neurodevelopmental disorder (Tanaka, 2017). Based on the available evidence, this alteration is classified as pathogenic. -
Hypotonia, ataxia, and delayed development syndrome Pathogenic:1
Criteria applied: PVS1,PM2,PS2_MOD,PS4_SUP -
not provided Pathogenic:1
Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 29162653) -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at