NM_003202.5:c.37G>C

Variant names:

• chr5-134114943-G-C
• rs1237423250
• NM_003202.5:c.37G>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_003202.5(TCF7):​c.37G>C​(p.Gly13Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000135 in 1,115,164 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000068 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: TCF7 NM_003202.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.49
• Publications: 0 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 14 AD gene.

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.37G>C	p.Gly13Arg	missense	Exon 1 of 10	NP_003193.2
	TCF7	NM_001346425.2		c.37G>C	p.Gly13Arg	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.37G>C	p.Gly13Arg	missense	Exon 1 of 10	ENSP00000340347.5	P36402-5
	TCF7	ENST00000395029.5	TSL:5	c.37G>C	p.Gly13Arg	missense	Exon 1 of 11	ENSP00000378472.1	B7WNT5
	TCF7	ENST00000851078.1		c.37G>C	p.Gly13Arg	missense	Exon 1 of 10	ENSP00000521137.1

Frequencies

GnomAD3 genomes AF: 0.00000683 AC: 1 AN: 146452 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000152

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000145 AC: 14 AN: 968712 Hom.: 0 Cov.: 31 AF XY: 0.0000150 AC XY: 7 AN XY: 465236

African (AFR) AF: 0.00 AC: 0 AN: 18580

American (AMR) AF: 0.00 AC: 0 AN: 10282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10918

East Asian (EAS) AF: 0.00 AC: 0 AN: 9370

South Asian (SAS) AF: 0.00 AC: 0 AN: 40250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9894

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2192

European-Non Finnish (NFE) AF: 0.0000168 AC: 14 AN: 833828

Other (OTH) AF: 0.00 AC: 0 AN: 33398

GnomAD4 genome AF: 0.00000683 AC: 1 AN: 146452 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 71206

African (AFR) AF: 0.00 AC: 0 AN: 40842

American (AMR) AF: 0.00 AC: 0 AN: 14778

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3388

East Asian (EAS) AF: 0.00 AC: 0 AN: 5086

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8516

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 308

European-Non Finnish (NFE) AF: 0.0000152 AC: 1 AN: 65796

Other (OTH) AF: 0.00 AC: 0 AN: 2018

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

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	Uncertain	0.54
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.36	T
Eigen	Benign	0.035
Eigen_PC	Benign	0.022
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.70	T
M_CAP	Pathogenic	0.99	D
MetaRNN	Uncertain	0.50	D
MetaSVM	Pathogenic	1.1	D
MutationAssessor	Benign	1.9	L
PhyloP100		4.5
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	-0.64	N
REVEL	Uncertain	0.59
Sift	Uncertain	0.022	D
Sift4G	Benign	0.061	T
Polyphen		0.44	B
Vest4		0.27
MutPred		0.69		Gain of methylation at G13 (P = 0.0138)
MVP		0.94
MPC		0.25
ClinPred		0.64	D
GERP RS		2.4
PromoterAI		0.064	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.6
gMVP		0.055
Mutation Taster		=82/18	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: rs1237423250; hg19: chr5-133450634;