NM_001367943.1:c.45C>A

Variant names:

• chr10-112950801-C-A
• rs76088094
• NM_001367943.1:c.45C>A

Variant summary

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

The NM_001367943.1(TCF7L2):​c.45C>A​(p.Asn15Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TCF7L2 NM_001367943.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.30

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 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	c.45C>A	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	c.45C>A	p.Asn15Lys	missense_variant	Exon 1 of 15	1	NM_001367943.1	ENSP00000348274.4

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1441306 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 714738

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: 0.00

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.84
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Pathogenic	28
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	0.65	D
LIST_S2	Uncertain	0.91	D;D;D;D;D;D;D;D;D;D;D;D
M_CAP	Pathogenic	0.65	D
MetaRNN	Uncertain	0.69	D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Pathogenic	1.1	D
MutationAssessor	Uncertain	2.6	.;.;M;M;.;M;M;M;M;.;.;.
PrimateAI	Pathogenic	0.91	D
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	D
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

Other links and lift over

dbSNP: rs76088094; hg19: chr10-114710560;