Variant 10-112950801-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001367943.1(TCF7L2):c.45C>G(p.Asn15Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000000694 in 1,441,306 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 29)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

TCF7L2
NM_001367943.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.30

Variant links:

Genes affected

TCF7L2 (HGNC:11641): (transcription factor 7 like 2) This gene encodes a high mobility group (HMG) box-containing transcription factor that plays a key role in the Wnt signaling pathway. The protein has been implicated in blood glucose homeostasis. Genetic variants of this gene are associated with increased risk of type 2 diabetes. Several transcript variants encoding multiple different isoforms have been found for this gene.[provided by RefSeq, Oct 2010]

TCF7L2 links:

ENSG00000233547 (HGNC:):

ENSG00000233547 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCF7L2	NM_001367943.1 link	c.45C>G	p.Asn15Lys	missense_variant	Exon 1 of 15	ENST00000355995.9	NP_001354872.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCF7L2	ENST00000355995.9 link	c.45C>G	p.Asn15Lys	missense_variant	Exon 1 of 15	1	NM_001367943.1	ENSP00000348274.4		Q9NQB0-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000455

AC:

AN:

219846

Hom.:

AF XY:

0.00000844

AC XY:

AN XY:

118430

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000363

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.94e-7

AC:

AN:

1441306

Hom.:

Cov.:

AF XY:

0.00000140

AC XY:

AN XY:

714738

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000168

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000827

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.84

BayesDel_addAF

Uncertain

0.097

BayesDel_noAF

Uncertain

0.010

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.089

T;T;D;.;T;.;.;.;.;T;.;T

Eigen

Uncertain

0.62

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Benign

0.66

LIST_S2

Uncertain

0.91

D;D;D;D;D;D;D;D;D;D;D;D

M_CAP

Pathogenic

0.64

MetaRNN

Uncertain

0.68

D;D;D;D;D;D;D;D;D;D;D;D

MetaSVM

Pathogenic

1.1

MutationAssessor

Uncertain

2.6

.;.;M;M;.;M;M;M;M;.;.;.

PrimateAI

Pathogenic

0.91

PROVEAN

Uncertain

-2.9

D;D;D;D;D;.;D;D;D;D;D;.

REVEL

Pathogenic

0.84

Sift

Uncertain

0.0080

D;D;D;D;D;.;D;D;D;D;D;.

Sift4G

Benign

0.065

T;D;D;D;D;D;D;D;D;D;T;D

Polyphen

0.98, 1.0, 0.99

.;D;.;.;.;D;.;.;.;.;D;.

Vest4

0.45

MutPred

0.51

Gain of ubiquitination at N15 (P = 0.0039);Gain of ubiquitination at N15 (P = 0.0039);Gain of ubiquitination at N15 (P = 0.0039);Gain of ubiquitination at N15 (P = 0.0039);Gain of ubiquitination at N15 (P = 0.0039);Gain of ubiquitination at N15 (P = 0.0039);Gain of ubiquitination at N15 (P = 0.0039);Gain of ubiquitination at N15 (P = 0.0039);Gain of ubiquitination at N15 (P = 0.0039);Gain of ubiquitination at N15 (P = 0.0039);Gain of ubiquitination at N15 (P = 0.0039);Gain of ubiquitination at N15 (P = 0.0039);

MVP

0.95

MPC

1.7

ClinPred

0.99

GERP RS

3.5

Varity_R

0.85

gMVP

0.47

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over