chr15-56919972-TA-T
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_207037.2(TCF12):c.60del(p.Leu21TrpfsTer66) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: not found (cov: 31)
Consequence
TCF12
NM_207037.2 frameshift
NM_207037.2 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 4.30
Genes affected
TCF12 (HGNC:11623): (transcription factor 12) The protein encoded by this gene is a member of the basic helix-loop-helix (bHLH) E-protein family that recognizes the consensus binding site (E-box) CANNTG. This encoded protein is expressed in many tissues, among them skeletal muscle, thymus, B- and T-cells, and may participate in regulating lineage-specific gene expression through the formation of heterodimers with other bHLH E-proteins. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 69 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 15-56919972-TA-T is Pathogenic according to our data. Variant chr15-56919972-TA-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 817307.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TCF12 | NM_207037.2 | c.60del | p.Leu21TrpfsTer66 | frameshift_variant | 2/21 | ENST00000333725.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TCF12 | ENST00000333725.10 | c.60del | p.Leu21TrpfsTer66 | frameshift_variant | 2/21 | 1 | NM_207037.2 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 genomes
?
Cov.:
31
GnomAD4 exome Cov.: 30
GnomAD4 exome
Cov.:
30
GnomAD4 genome ? Cov.: 31
GnomAD4 genome
?
Cov.:
31
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Nov 06, 2018 | A variant that is likely pathogenic has been identified in the TCF12 gene. The c.60delA variant causes a frameshift starting with codon Leucine 21, changes this amino acid to a Tryptophan residue and creates a premature Stop codon at position 66 of the new reading frame, denoted p.Leu21TrpfsX66. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.60delA variant is not observed in large population cohorts (Lek et al., 2016). Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at