chr20-604655-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_004609.4(TCF15):c.536G>A(p.Arg179His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000271 in 1,552,072 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00016 ( 1 hom., cov: 32)
Exomes 𝑓: 0.000013 ( 0 hom. )
Consequence
TCF15
NM_004609.4 missense
NM_004609.4 missense
Scores
1
13
5
Clinical Significance
Conservation
PhyloP100: 1.56
Genes affected
TCF15 (HGNC:11627): (transcription factor 15) The protein encoded by this gene is found in the nucleus and may be involved in the early transcriptional regulation of patterning of the mesoderm. The encoded basic helix-loop-helix protein requires dimerization with another basic helix-loop-helix protein for efficient DNA binding. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.3377055).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TCF15 | NM_004609.4 | c.536G>A | p.Arg179His | missense_variant | 2/2 | ENST00000246080.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TCF15 | ENST00000246080.4 | c.536G>A | p.Arg179His | missense_variant | 2/2 | 1 | NM_004609.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000158 AC: 24AN: 152110Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.0000128 AC: 2AN: 155948Hom.: 0 AF XY: 0.0000121 AC XY: 1AN XY: 82346
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GnomAD4 exome AF: 0.0000129 AC: 18AN: 1399962Hom.: 0 Cov.: 30 AF XY: 0.0000130 AC XY: 9AN XY: 690638
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GnomAD4 genome AF: 0.000158 AC: 24AN: 152110Hom.: 1 Cov.: 32 AF XY: 0.000135 AC XY: 10AN XY: 74304
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 05, 2024 | The c.536G>A (p.R179H) alteration is located in exon 2 (coding exon 2) of the TCF15 gene. This alteration results from a G to A substitution at nucleotide position 536, causing the arginine (R) at amino acid position 179 to be replaced by a histidine (H). 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
Uncertain
DANN
Pathogenic
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Uncertain
D
MetaRNN
Benign
T
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M
MutationTaster
Benign
N
PrimateAI
Uncertain
T
PROVEAN
Uncertain
N
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MutPred
Loss of MoRF binding (P = 0.0315);
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