Variant rs4135113 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003211.6(TDG):c.595G>A(p.Gly199Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0333 in 1,613,864 control chromosomes in the GnomAD database, including 2,104 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.071 ( 725 hom., cov: 32)

Exomes 𝑓: 0.029 ( 1379 hom. )

Consequence

TDG
NM_003211.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.86

Variant links:

Genes affected

TDG (HGNC:11700): (thymine DNA glycosylase) The protein encoded by this gene belongs to the TDG/mug DNA glycosylase family. Thymine-DNA glycosylase (TDG) removes thymine moieties from G/T mismatches by hydrolyzing the carbon-nitrogen bond between the sugar-phosphate backbone of DNA and the mispaired thymine. With lower activity, this enzyme also removes thymine from C/T and T/T mispairings. TDG can also remove uracil and 5-bromouracil from mispairings with guanine. This enzyme plays a central role in cellular defense against genetic mutation caused by the spontaneous deamination of 5-methylcytosine and cytosine. This gene may have a pseudogene in the p arm of chromosome 12. [provided by RefSeq, Jul 2008]

TDG links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0018633008).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.163 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TDG	NM_003211.6 linkuse as main transcript	c.595G>A	p.Gly199Ser	missense_variant	5/10	ENST00000392872.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TDG	ENST00000392872.8 linkuse as main transcript	c.595G>A	p.Gly199Ser	missense_variant	5/10	1	NM_003211.6	P1

Frequencies

GnomAD3 genomes

AF:

0.0713

AC:

10835

AN:

152022

Hom.:

721

Cov.:

show subpopulations

Gnomad AFR

AF:

0.167

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0703

Gnomad ASJ

AF:

0.0680

Gnomad EAS

AF:

0.150

Gnomad SAS

AF:

0.0262

Gnomad FIN

AF:

0.0191

Gnomad MID

AF:

0.127

Gnomad NFE

AF:

0.0197

Gnomad OTH

AF:

0.0738

GnomAD3 exomes

AF:

0.0467

AC:

11729

AN:

251310

Hom.:

306

AF XY:

0.0429

AC XY:

5820

AN XY:

135816

show subpopulations

Gnomad AFR exome

AF:

0.160

Gnomad AMR exome

AF:

0.0573

Gnomad ASJ exome

AF:

0.0651

Gnomad EAS exome

AF:

0.144

Gnomad SAS exome

AF:

0.0246

Gnomad FIN exome

AF:

0.0206

Gnomad NFE exome

AF:

0.0208

Gnomad OTH exome

AF:

0.0454

GnomAD4 exome

AF:

0.0293

AC:

42814

AN:

1461724

Hom.:

1379

Cov.:

AF XY:

0.0291

AC XY:

21133

AN XY:

727176

show subpopulations

Gnomad4 AFR exome

AF:

0.169

Gnomad4 AMR exome

AF:

0.0564

Gnomad4 ASJ exome

AF:

0.0613

Gnomad4 EAS exome

AF:

0.167

Gnomad4 SAS exome

AF:

0.0254

Gnomad4 FIN exome

AF:

0.0191

Gnomad4 NFE exome

AF:

0.0182

Gnomad4 OTH exome

AF:

0.0427

GnomAD4 genome

AF:

0.0713

AC:

10847

AN:

152140

Hom.:

725

Cov.:

AF XY:

0.0715

AC XY:

5314

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.166

Gnomad4 AMR

AF:

0.0702

Gnomad4 ASJ

AF:

0.0680

Gnomad4 EAS

AF:

0.150

Gnomad4 SAS

AF:

0.0264

Gnomad4 FIN

AF:

0.0191

Gnomad4 NFE

AF:

0.0197

Gnomad4 OTH

AF:

0.0731

Alfa

AF:

0.0345

Hom.:

393

Bravo

AF:

0.0800

TwinsUK

AF:

0.0178

AC:

ALSPAC

AF:

0.0150

AC:

ESP6500AA

AF:

0.164

AC:

721

ESP6500EA

AF:

0.0237

AC:

204

ExAC

AF:

0.0467

AC:

5675

Asia WGS

AF:

0.0810

AC:

284

AN:

3478

EpiCase

AF:

0.0250

EpiControl

AF:

0.0256

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.86

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.48

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.32

T;.;.;T

Eigen

Benign

-0.019

Eigen_PC

Benign

0.073

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.85

T;T;T;T

MetaRNN

Benign

0.0019

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

L;.;.;.

MutationTaster

Benign

1.8e-9

P;P;P;P

PrimateAI

Uncertain

0.76

PROVEAN

Pathogenic

-5.5

D;D;D;D

REVEL

Benign

0.22

Sift

Benign

0.21

T;T;T;T

Sift4G

Benign

0.20

T;T;T;T

Polyphen

0.43

B;.;.;.

Vest4

0.20

MPC

0.63

ClinPred

0.067

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.75

gMVP

0.86

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over