chr15-57063807-C-T
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4
The NM_207037.2(TCF12):c.206C>T(p.Ser69Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000749 in 1,602,486 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000069 ( 0 hom. )
Consequence
TCF12
NM_207037.2 missense
NM_207037.2 missense
Scores
3
7
7
Clinical Significance
Conservation
PhyloP100: 4.87
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 Likely_benign. Variant got -1 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.4040411).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TCF12 | NM_207037.2 | c.206C>T | p.Ser69Phe | missense_variant | 4/21 | ENST00000333725.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TCF12 | ENST00000333725.10 | c.206C>T | p.Ser69Phe | missense_variant | 4/21 | 1 | NM_207037.2 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152174Hom.: 0 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251292Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135826
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GnomAD4 exome AF: 0.00000690 AC: 10AN: 1450312Hom.: 0 Cov.: 30 AF XY: 0.00000555 AC XY: 4AN XY: 720188
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GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152174Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74338
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 29, 2021 | The c.206C>T (p.S69F) alteration is located in exon 4 (coding exon 3) of the TCF12 gene. This alteration results from a C to T substitution at nucleotide position 206, causing the serine (S) at amino acid position 69 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;M;M;.
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D;D;D
REVEL
Benign
Sift
Pathogenic
D;D;D;D;D
Sift4G
Benign
T;T;T;T;T
Polyphen
D;D;D;D;.
Vest4
MutPred
Loss of phosphorylation at S69 (P = 0.0075);Loss of phosphorylation at S69 (P = 0.0075);Loss of phosphorylation at S69 (P = 0.0075);Loss of phosphorylation at S69 (P = 0.0075);Loss of phosphorylation at S69 (P = 0.0075);
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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