NM_003202.5:c.314A>G

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4BS2

The NM_003202.5(TCF7):c.314A>G(p.Asp105Gly) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000563 in 1,599,950 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

TCF7
NM_003202.5 missense, splice_region

Scores

Splicing: ADA: 0.002512

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.23

Publications

0 publications found

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]

TCF7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.34650886).

BS2

High AC in GnomAdExome4 at 7 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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
TCF7	NM_003202.5	MANE Select	c.314A>G	p.Asp105Gly	missense splice_region	Exon 2 of 10	NP_003193.2
TCF7	NM_001346425.2		c.314A>G	p.Asp105Gly	missense splice_region	Exon 2 of 11	NP_001333354.1
TCF7	NM_001346450.2		c.-319A>G		upstream_gene	N/A	NP_001333379.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TCF7	ENST00000342854.10	TSL:1 MANE Select	c.314A>G	p.Asp105Gly	missense splice_region	Exon 2 of 10	ENSP00000340347.5	P36402-5
TCF7	ENST00000395029.5	TSL:5	c.314A>G	p.Asp105Gly	missense splice_region	Exon 2 of 11	ENSP00000378472.1	B7WNT5
TCF7	ENST00000851078.1		c.314A>G	p.Asp105Gly	missense splice_region	Exon 2 of 10	ENSP00000521137.1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151916

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000484

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000889

AC:

AN:

224916

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.000149

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

0.00000483

AC:

AN:

1448034

Hom.:

Cov.:

AF XY:

0.00000556

AC XY:

AN XY:

719274

show subpopulations

African (AFR)

AF:

0.000212

AC:

AN:

32984

American (AMR)

AF:

0.00

AC:

AN:

43596

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25808

East Asian (EAS)

AF:

0.00

AC:

AN:

39018

South Asian (SAS)

AF:

0.00

AC:

AN:

83910

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51164

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5614

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1106134

Other (OTH)

AF:

0.00

AC:

AN:

59806

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151916

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74196

show subpopulations

African (AFR)

AF:

0.0000484

AC:

AN:

41342

American (AMR)

AF:

0.00

AC:

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5154

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10592

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67958

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000658

Hom.:

Bravo

AF:

0.0000264

ESP6500AA

AF:

0.000455

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000166

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Uncertain

-0.040

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.32

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.085

FATHMM_MKL

Benign

0.30

LIST_S2

Benign

0.72

M_CAP

Pathogenic

0.95

MetaRNN

Benign

0.35

MetaSVM

Pathogenic

0.87

MutationAssessor

Benign

0.90

PhyloP100

3.2

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-1.9

REVEL

Uncertain

0.51

Sift

Benign

0.091

Sift4G

Benign

0.23

Polyphen

0.0020

Vest4

0.46

MVP

0.92

MPC

0.28

ClinPred

0.14

GERP RS

3.7

PromoterAI

-0.034

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

gMVP

0.48

Mutation Taster

=81/19

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0025

dbscSNV1_RF

Benign

0.16

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over