Variant 6-133889460-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_003206.4(TCF21):c.63C>G(p.Asp21Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00867 in 1,614,060 control chromosomes in the GnomAD database, including 84 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: 𝑓 0.0059 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0090 ( 82 hom. )

Consequence

TCF21
NM_003206.4 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: -0.402

Variant links:

Genes affected

TCF21 (HGNC:11632): (transcription factor 21) TCF21 encodes a transcription factor of the basic helix-loop-helix family. The TCF21 product is mesoderm specific, and expressed in embryonic epicardium, mesenchyme-derived tissues of lung, gut, gonad, and both mesenchymal and glomerular epithelial cells in the kidney. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

TCF21 links:

TARID (HGNC:50506): (TCF21 antisense RNA inducing promoter demethylation)

TARID links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0035883188).

BS2

High AC in GnomAd at 894 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TCF21	NM_003206.4 linkuse as main transcript	c.63C>G	p.Asp21Glu	missense_variant	1/2	ENST00000367882.5
TCF21	NM_198392.3 linkuse as main transcript	c.63C>G	p.Asp21Glu	missense_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TCF21	ENST00000367882.5 linkuse as main transcript	c.63C>G	p.Asp21Glu	missense_variant	1/2	1	NM_003206.4	P1

Frequencies

GnomAD3 genomes

AF:

0.00588

AC:

894

AN:

152050

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00246

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00510

Gnomad ASJ

AF:

0.00403

Gnomad EAS

AF:

0.00136

Gnomad SAS

AF:

0.00269

Gnomad FIN

AF:

0.00321

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00933

Gnomad OTH

AF:

0.00574

GnomAD3 exomes

AF:

0.00587

AC:

1476

AN:

251472

Hom.:

AF XY:

0.00604

AC XY:

821

AN XY:

135908

show subpopulations

Gnomad AFR exome

AF:

0.00148

Gnomad AMR exome

AF:

0.00269

Gnomad ASJ exome

AF:

0.00387

Gnomad EAS exome

AF:

0.000272

Gnomad SAS exome

AF:

0.00294

Gnomad FIN exome

AF:

0.00411

Gnomad NFE exome

AF:

0.00957

Gnomad OTH exome

AF:

0.00766

GnomAD4 exome

AF:

0.00896

AC:

13096

AN:

1461892

Hom.:

Cov.:

AF XY:

0.00856

AC XY:

6222

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00122

Gnomad4 AMR exome

AF:

0.00273

Gnomad4 ASJ exome

AF:

0.00291

Gnomad4 EAS exome

AF:

0.000327

Gnomad4 SAS exome

AF:

0.00294

Gnomad4 FIN exome

AF:

0.00522

Gnomad4 NFE exome

AF:

0.0107

Gnomad4 OTH exome

AF:

0.00684

GnomAD4 genome

AF:

0.00588

AC:

894

AN:

152168

Hom.:

Cov.:

AF XY:

0.00556

AC XY:

414

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.00246

Gnomad4 AMR

AF:

0.00510

Gnomad4 ASJ

AF:

0.00403

Gnomad4 EAS

AF:

0.00136

Gnomad4 SAS

AF:

0.00269

Gnomad4 FIN

AF:

0.00321

Gnomad4 NFE

AF:

0.00933

Gnomad4 OTH

AF:

0.00568

Alfa

AF:

0.00875

Hom.:

Bravo

AF:

0.00571

TwinsUK

AF:

0.0102

AC:

ALSPAC

AF:

0.0127

AC:

ESP6500AA

AF:

0.00204

AC:

ESP6500EA

AF:

0.00779

AC:

ExAC

AF:

0.00570

AC:

692

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.00987

EpiControl

AF:

0.00848

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

OMIM

Dec 01, 2014

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.26

Cadd

Benign

8.3

Dann

Benign

0.90

DEOGEN2

Benign

0.16

T;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.38

MetaRNN

Benign

0.0036

T;T

MetaSVM

Benign

-0.41

MutationAssessor

Benign

0.55

N;N

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.44

N;N

REVEL

Benign

0.23

Sift

Benign

0.39

T;T

Sift4G

Benign

0.60

T;T

Polyphen

0.14

B;B

Vest4

0.044

MutPred

0.68

Gain of helix (P = 0.0225);Gain of helix (P = 0.0225);

MVP

0.58

MPC

0.66

ClinPred

0.0015

GERP RS

0.58

Varity_R

0.041

gMVP

0.12

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over