Genetic Variant TDG:c.965-58G>C (chr12-103985545-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003211.6(TDG):c.965-58G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0913 in 1,534,176 control chromosomes in the GnomAD database, including 7,489 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.

Frequency

Genomes: 𝑓 0.080 ( 691 hom., cov: 32)

Exomes 𝑓: 0.093 ( 6798 hom. )

Consequence

TDG
NM_003211.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.134

Publications

9 publications found

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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TDG	NM_003211.6 link	c.965-58G>C		intron_variant	Intron 8 of 9	ENST00000392872.8	NP_003202.3	Q13569B4E127

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TDG	ENST00000392872.8 link	c.965-58G>C		intron_variant	Intron 8 of 9	1	NM_003211.6	ENSP00000376611.3		Q13569

Frequencies

GnomAD3 genomes

AF:

0.0803

AC:

12223

AN:

152126

Hom.:

691

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0291

Gnomad AMI

AF:

0.0811

Gnomad AMR

AF:

0.0533

Gnomad ASJ

AF:

0.118

Gnomad EAS

AF:

0.214

Gnomad SAS

AF:

0.159

Gnomad FIN

AF:

0.141

Gnomad MID

AF:

0.120

Gnomad NFE

AF:

0.0904

Gnomad OTH

AF:

0.0784

GnomAD4 exome

AF:

0.0925

AC:

127877

AN:

1381932

Hom.:

6798

AF XY:

0.0951

AC XY:

65063

AN XY:

684124

show subpopulations

African (AFR)

AF:

0.0291

AC:

896

AN:

30804

American (AMR)

AF:

0.0379

AC:

1305

AN:

34438

Ashkenazi Jewish (ASJ)

AF:

0.110

AC:

2518

AN:

22790

East Asian (EAS)

AF:

0.209

AC:

7978

AN:

38166

South Asian (SAS)

AF:

0.154

AC:

11137

AN:

72470

European-Finnish (FIN)

AF:

0.126

AC:

6442

AN:

50972

Middle Eastern (MID)

AF:

0.132

AC:

557

AN:

4212

European-Non Finnish (NFE)

AF:

0.0855

AC:

91571

AN:

1071100

Other (OTH)

AF:

0.0961

AC:

5473

AN:

56980

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

5360

10720

16079

21439

26799

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3506

7012

10518

14024

17530

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0803

AC:

12229

AN:

152244

Hom.:

691

Cov.:

AF XY:

0.0844

AC XY:

6284

AN XY:

74424

show subpopulations

African (AFR)

AF:

0.0291

AC:

1209

AN:

41554

American (AMR)

AF:

0.0531

AC:

813

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.118

AC:

409

AN:

3472

East Asian (EAS)

AF:

0.216

AC:

1114

AN:

5168

South Asian (SAS)

AF:

0.160

AC:

772

AN:

4832

European-Finnish (FIN)

AF:

0.141

AC:

1490

AN:

10594

Middle Eastern (MID)

AF:

0.119

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0904

AC:

6150

AN:

67998

Other (OTH)

AF:

0.0771

AC:

163

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

568

1136

1703

2271

2839

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

152

304

456

608

760

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0833

Hom.:

Bravo

AF:

0.0721

Asia WGS

AF:

0.170

AC:

592

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

1.6

(source)

DANN

Benign

0.56

PhyloP100

0.13

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over