5-134115992-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_003202.5(TCF7):​c.400C>T​(p.Pro134Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,613,554 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

TCF7
NM_003202.5 missense

Scores

3
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.71
Variant links:
Genes affected
TCF7 (HGNC:11639): (transcription factor 7) This gene encodes a member of the T-cell factor/lymphoid enhancer-binding factor family of high mobility group (HMG) box transcriptional activators. This gene is expressed predominantly in T-cells and plays a critical role in natural killer cell and innate lymphoid cell development. The encoded protein forms a complex with beta-catenin and activates transcription through a Wnt/beta-catenin signaling pathway. Mice with a knockout of this gene are viable and fertile, but display a block in T-lymphocyte differentiation. Alternative splicing results in multiple transcript variants. Naturally-occurring isoforms lacking the N-terminal beta-catenin interaction domain may act as dominant negative regulators of Wnt signaling. [provided by RefSeq, Oct 2016]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.06779027).
BS2
High AC in GnomAdExome4 at 14 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TCF7NM_003202.5 linkc.400C>T p.Pro134Ser missense_variant Exon 3 of 10 ENST00000342854.10 NP_003193.2 P36402-5B3KQ75

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TCF7ENST00000342854.10 linkc.400C>T p.Pro134Ser missense_variant Exon 3 of 10 1 NM_003202.5 ENSP00000340347.5 P36402-5

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152216
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000724
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000120
AC:
3
AN:
249658
Hom.:
0
AF XY:
0.0000148
AC XY:
2
AN XY:
135414
show subpopulations
Gnomad AFR exome
AF:
0.000124
Gnomad AMR exome
AF:
0.0000290
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000958
AC:
14
AN:
1461338
Hom.:
0
Cov.:
33
AF XY:
0.0000124
AC XY:
9
AN XY:
726962
show subpopulations
Gnomad4 AFR exome
AF:
0.0000597
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000464
Gnomad4 FIN exome
AF:
0.0000378
Gnomad4 NFE exome
AF:
0.00000360
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152216
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
AN XY:
74358
show subpopulations
Gnomad4 AFR
AF:
0.0000724
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.00226
Hom.:
933
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.10
T
BayesDel_noAF
Benign
-0.15
CADD
Benign
0.022
DANN
Benign
0.91
DEOGEN2
Benign
0.27
.;T;T;.;.;T;.;.;.;.
Eigen
Benign
-2.6
Eigen_PC
Benign
-2.7
FATHMM_MKL
Benign
0.022
N
LIST_S2
Benign
0.77
T;T;T;T;T;T;T;.;T;T
M_CAP
Uncertain
0.29
D
MetaRNN
Benign
0.068
T;T;T;T;T;T;T;T;T;T
MetaSVM
Uncertain
0.30
D
MutationAssessor
Benign
0.0
N;.;.;.;.;.;.;.;.;.
PrimateAI
Benign
0.29
T
PROVEAN
Benign
0.19
N;N;N;N;N;N;N;N;N;N
REVEL
Uncertain
0.37
Sift
Benign
0.51
T;T;D;D;T;D;T;T;T;T
Sift4G
Benign
0.46
T;T;T;T;D;T;T;T;T;T
Polyphen
0.0
B;B;.;.;.;.;.;.;.;.
Vest4
0.19
MutPred
0.54
Loss of catalytic residue at P133 (P = 0.062);Loss of catalytic residue at P133 (P = 0.062);.;.;.;.;.;.;.;.;
MVP
0.52
MPC
0.24
ClinPred
0.024
T
GERP RS
-10
gMVP
0.37

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs5742913; hg19: chr5-133451683; API