2-85283531-T-C

Variant names:

• chr2-85283531-T-C
• NM_031283.3:c.478T>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_031283.3(TCF7L1):​c.478T>C​(p.Ser160Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,876 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TCF7L1 NM_031283.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0630

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3806818).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCF7L1	NM_031283.3	c.478T>C	p.Ser160Pro	missense_variant	Exon 4 of 12	ENST00000282111.4	NP_112573.1
TCF7L1	XM_006712109.3	c.478T>C	p.Ser160Pro	missense_variant	Exon 4 of 12		XP_006712172.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCF7L1	ENST00000282111.4	c.478T>C	p.Ser160Pro	missense_variant	Exon 4 of 12	1	NM_031283.3	ENSP00000282111.3
TCF7L1	ENST00000442813.1	c.28T>C	p.Ser10Pro	missense_variant	Exon 5 of 6	5		ENSP00000388984.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461876 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727238

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T;.
Eigen	Benign	-0.074
Eigen_PC	Benign	-0.0027
FATHMM_MKL	Benign	0.54	D
LIST_S2	Benign	0.75	T;T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.38	T;T
MetaSVM	Uncertain	0.59	D
MutationAssessor	Benign	1.8	L;.
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.89	N;D
REVEL	Uncertain	0.47
Sift	Uncertain	0.012	D;T
Sift4G	Benign	0.38	T;T
Polyphen		0.76	P;.
Vest4		0.40
MutPred		0.58		Gain of catalytic residue at P159 (P = 0.0186);.;
MVP		0.74
MPC		0.72
ClinPred		0.58	D
GERP RS		3.1
Varity_R		0.17
gMVP		0.31

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: chr2-85510654;