10-112950840-G-T

Variant names:

• chr10-112950840-G-T
• NM_001367943.1:c.84G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001367943.1(TCF7L2):​c.84G>T​(p.Glu28Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 29)
• Consequence: TCF7L2 NM_001367943.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.01

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]

ENSG00000233547 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25341833).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCF7L2	NM_001367943.1	c.84G>T	p.Glu28Asp	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	c.84G>T	p.Glu28Asp	missense_variant	Exon 1 of 15	1	NM_001367943.1	ENSP00000348274.4

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.035	T;T;T;.;T;.;.;.;.;T;.;T
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.066
FATHMM_MKL	Benign	0.36	N
LIST_S2	Uncertain	0.91	D;D;D;D;D;D;D;D;D;D;D;D
M_CAP	Pathogenic	0.47	D
MetaRNN	Benign	0.25	T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Pathogenic	0.90	D
MutationAssessor	Benign	1.5	.;.;L;L;.;L;L;L;L;.;.;.
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-1.8	N;N;N;N;N;.;N;N;N;N;N;.
REVEL	Uncertain	0.47
Sift	Benign	0.046	D;D;D;D;D;.;T;D;T;T;D;.
Sift4G	Benign	0.11	T;T;T;T;T;T;T;T;T;D;T;T
Polyphen		0.011, 0.022, 0.0080	.;B;.;.;.;B;.;.;.;.;B;.
Vest4		0.33
MutPred		0.33		Loss of solvent accessibility (P = 0.1177);Loss of solvent accessibility (P = 0.1177);Loss of solvent accessibility (P = 0.1177);Loss of solvent accessibility (P = 0.1177);Loss of solvent accessibility (P = 0.1177);Loss of solvent accessibility (P = 0.1177);Loss of solvent accessibility (P = 0.1177);Loss of solvent accessibility (P = 0.1177);Loss of solvent accessibility (P = 0.1177);Loss of solvent accessibility (P = 0.1177);Loss of solvent accessibility (P = 0.1177);Loss of solvent accessibility (P = 0.1177);
MVP		0.83
MPC		0.69
ClinPred		0.71	D
GERP RS		3.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.54
gMVP		0.18

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.

Other links and lift over

hg19: chr10-114710599;