Variant chr10-112950906-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001367943.1(TCF7L2):c.150T>A(p.Asn50Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000137 in 1,460,362 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: 0.000014 ( 0 hom. )

Consequence

TCF7L2
NM_001367943.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.31

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 Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAdExome4 at 20 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCF7L2	NM_001367943.1 link	c.150T>A	p.Asn50Lys	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.150T>A	p.Asn50Lys	missense_variant	Exon 1 of 15	1	NM_001367943.1	ENSP00000348274.4		Q9NQB0-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000137

AC:

AN:

1460362

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

726330

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:

0.0000180

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

Inborn genetic diseases

Uncertain:1

Jun 21, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.150T>A (p.N50K) alteration is located in exon 1 (coding exon 1) of the TCF7L2 gene. This alteration results from a T to A substitution at nucleotide position 150, causing the asparagine (N) at amino acid position 50 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.99

BayesDel_addAF

Pathogenic

0.18

BayesDel_noAF

Uncertain

0.030

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

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

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Benign

0.34

LIST_S2

Uncertain

0.95

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

M_CAP

Pathogenic

0.93

MetaRNN

Uncertain

0.74

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

MetaSVM

Pathogenic

1.1

MutationAssessor

Uncertain

2.8

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

PrimateAI

Pathogenic

0.93

PROVEAN

Uncertain

-4.1

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

REVEL

Pathogenic

0.81

Sift

Uncertain

0.0010

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

Sift4G

Benign

0.24

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

Polyphen

1.0, 0.99, 1.0

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

Vest4

0.47

MutPred

0.56

Gain of ubiquitination at N50 (P = 0.0069);Gain of ubiquitination at N50 (P = 0.0069);Gain of ubiquitination at N50 (P = 0.0069);Gain of ubiquitination at N50 (P = 0.0069);Gain of ubiquitination at N50 (P = 0.0069);Gain of ubiquitination at N50 (P = 0.0069);Gain of ubiquitination at N50 (P = 0.0069);Gain of ubiquitination at N50 (P = 0.0069);Gain of ubiquitination at N50 (P = 0.0069);Gain of ubiquitination at N50 (P = 0.0069);Gain of ubiquitination at N50 (P = 0.0069);Gain of ubiquitination at N50 (P = 0.0069);

MVP

0.98

MPC

1.7

ClinPred

0.99

GERP RS

2.9

Varity_R

0.83

gMVP

0.55

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