5-134115118-T-G

Variant names:

• chr5-134115118-T-G
• rs1052562972
• NM_003202.5:c.212T>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_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. 16/21 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.192
• Publications: 1 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003202.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCF7	NM_003202.5	MANE Select	c.212T>G	p.Val71Gly	missense	Exon 1 of 10	NP_003193.2
	TCF7	NM_001346425.2		c.212T>G	p.Val71Gly	missense	Exon 1 of 11	NP_001333354.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCF7	ENST00000342854.10	TSL:1 MANE Select	c.212T>G	p.Val71Gly	missense	Exon 1 of 10	ENSP00000340347.5	P36402-5
	TCF7	ENST00000395029.5	TSL:5	c.212T>G	p.Val71Gly	missense	Exon 1 of 11	ENSP00000378472.1	B7WNT5
	TCF7	ENST00000851078.1		c.212T>G	p.Val71Gly	missense	Exon 1 of 10	ENSP00000521137.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
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
M_CAP	Benign	0.084	D
MetaRNN	Benign	0.13	T
MetaSVM	Uncertain	0.35	D
MutationAssessor	Benign	0.81	L
PhyloP100		0.19
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-0.31	N
REVEL	Benign	0.24
Sift	Benign	0.40	T
Sift4G	Benign	0.38	T
Polyphen		0.0	B
Vest4		0.20
MutPred		0.35		Loss of stability (P = 0.0139)
MVP		0.78
MPC		0.27
ClinPred		0.031	T
GERP RS		-1.2
PromoterAI		0.10	Neutral
gMVP		0.10
Mutation Taster		=89/11	polymorphism

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

Other links and lift over

dbSNP: rs1052562972; hg19: chr5-133450809;