5-134115118-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003202.5(TCF7):​c.212T>G​(p.Val71Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Consequence

TCF7
NM_003202.5 missense

Scores

1
1
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.192
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.12730831).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TCF7NM_003202.5 linkuse as main transcriptc.212T>G p.Val71Gly missense_variant 1/10 ENST00000342854.10 NP_003193.2 P36402-5B3KQ75

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TCF7ENST00000342854.10 linkuse as main transcriptc.212T>G p.Val71Gly missense_variant 1/101 NM_003202.5 ENSP00000340347.5 P36402-5
TCF7ENST00000395029.5 linkuse as main transcriptc.212T>G p.Val71Gly missense_variant 1/115 ENSP00000378472.1 B7WNT5

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
31

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 submitterclinical testingAmbry GeneticsNov 09, 2021The c.212T>G (p.V71G) alteration is located in exon 1 (coding exon 1) of the TCF7 gene. This alteration results from a T to G substitution at nucleotide position 212, causing the valine (V) at amino acid position 71 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.018
T
BayesDel_noAF
Benign
-0.26
CADD
Benign
11
DANN
Benign
0.68
DEOGEN2
Benign
0.28
.;T
Eigen
Benign
-1.0
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.0029
N
LIST_S2
Benign
0.22
T;T
M_CAP
Benign
0.084
D
MetaRNN
Benign
0.13
T;T
MetaSVM
Uncertain
0.35
D
MutationAssessor
Benign
0.81
L;.
PrimateAI
Pathogenic
0.88
D
PROVEAN
Benign
-0.31
N;N
REVEL
Benign
0.24
Sift
Benign
0.40
T;T
Sift4G
Benign
0.38
T;T
Polyphen
0.0
B;.
Vest4
0.20
MutPred
0.35
Loss of stability (P = 0.0139);Loss of stability (P = 0.0139);
MVP
0.78
MPC
0.27
ClinPred
0.031
T
GERP RS
-1.2
gMVP
0.10

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: rs1052562972; hg19: chr5-133450809; API