Variant 10-112951542-A-T 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.316A>T(p.Ile106Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000157 in 1,273,442 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 29)

Exomes 𝑓: 0.0000016 ( 0 hom. )

Consequence

TCF7L2
NM_001367943.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.00

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/exons	MANE	Protein	UniProt
TCF7L2	NM_001367943.1 link	c.316A>T	p.Ile106Phe	missense_variant	3/15	ENST00000355995.9	NP_001354872.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCF7L2	ENST00000355995.9 link	c.316A>T	p.Ile106Phe	missense_variant	3/15	1	NM_001367943.1	ENSP00000348274.4		Q9NQB0-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000157

AC:

AN:

1273442

Hom.:

Cov.:

AF XY:

0.00000315

AC XY:

AN XY:

634170

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:

0.00000200

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Jul 31, 2024

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis indicates that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.52

BayesDel_addAF

Pathogenic

0.18

BayesDel_noAF

Uncertain

0.020

CADD

Uncertain

DANN

Benign

0.88

DEOGEN2

Benign

0.029

T;T;T;.;T;.;.;.;.;T;.;T;T

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.52

FATHMM_MKL

Benign

0.14

LIST_S2

Uncertain

0.90

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

M_CAP

Pathogenic

0.98

MetaRNN

Uncertain

0.43

T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Pathogenic

0.91

MutationAssessor

Benign

1.1

.;.;L;L;.;L;L;L;L;.;.;.;.

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-1.5

N;N;N;N;N;.;N;N;N;N;N;.;N

REVEL

Uncertain

0.59

Sift

Benign

0.071

T;T;T;T;T;.;T;T;T;T;T;.;T

Sift4G

Benign

0.49

T;T;T;T;T;T;T;T;T;T;T;T;T

Polyphen

0.091, 0.0020, 0.21

.;B;.;.;.;B;.;.;.;.;B;.;.

Vest4

0.51

MutPred

0.46

Gain of sheet (P = 0.0125);Gain of sheet (P = 0.0125);Gain of sheet (P = 0.0125);Gain of sheet (P = 0.0125);Gain of sheet (P = 0.0125);Gain of sheet (P = 0.0125);Gain of sheet (P = 0.0125);Gain of sheet (P = 0.0125);Gain of sheet (P = 0.0125);Gain of sheet (P = 0.0125);Gain of sheet (P = 0.0125);Gain of sheet (P = 0.0125);.;

MVP

0.86

MPC

1.1

ClinPred

0.28

GERP RS

1.2

Varity_R

0.18

gMVP

0.51

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over