chr2-85133727-A-C

Variant names:

• chr2-85133727-A-C
• NM_031283.3:c.43A>C

Variant summary

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

The NM_031283.3(TCF7L1):​c.43A>C​(p.Ser15Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000966 in 1,035,100 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict 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: 32)
  • Exomes 𝑓: 9.7e-7 (0 hom.)
• Consequence: TCF7L1 NM_031283.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.41

Genes affected

TCF7L1 (HGNC:11640): (transcription factor 7 like 1) This gene encodes a member of the T cell factor/lymphoid enhancer factor family of transcription factors. These transcription factors are activated by beta catenin, mediate the Wnt signaling pathway and are antagonized by the transforming growth factor beta signaling pathway. The encoded protein contains a high mobility group-box DNA binding domain and participates in the regulation of cell cycle genes and cellular senescence. [provided by RefSeq, Nov 2010]

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=0.14605904).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCF7L1	NM_031283.3	c.43A>C	p.Ser15Arg	missense_variant	Exon 1 of 12	ENST00000282111.4	NP_112573.1
TCF7L1	XM_006712109.3	c.43A>C	p.Ser15Arg	missense_variant	Exon 1 of 12		XP_006712172.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCF7L1	ENST00000282111.4	c.43A>C	p.Ser15Arg	missense_variant	Exon 1 of 12	1	NM_031283.3	ENSP00000282111.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 9.66e-7 AC: 1 AN: 1035100 Hom.: 0 Cov.: 32 AF XY: 0.00000204 AC XY: 1 AN XY: 489646

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: 0.00000113

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Uncertain	0.066	T
BayesDel_noAF	Benign	-0.14
CADD	Benign	16
DANN	Benign	0.28
DEOGEN2	Benign	0.088	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.029	N
LIST_S2	Benign	0.21	T
M_CAP	Pathogenic	0.39	D
MetaRNN	Benign	0.15	T
MetaSVM	Uncertain	0.054	D
MutationAssessor	Benign	-0.55	N
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.090	N
REVEL	Uncertain	0.36
Sift	Benign	0.060	T
Sift4G	Benign	0.53	T
Polyphen		0.0	B
Vest4		0.18
MutPred		0.45		Loss of phosphorylation at S15 (P = 0.0011);
MVP		0.56
MPC		1.3
ClinPred		0.043	T
GERP RS		0.82
Varity_R		0.073
gMVP		0.45

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: chr2-85360850;