Genetic Variant ENST00000544060.1:n.1135A>G (chr12-103980664-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000544060.1(TDG):n.1135A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.425 in 414,542 control chromosomes in the GnomAD database, including 42,741 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 0.40 ( 14269 hom., cov: 32)

Exomes 𝑓: 0.44 ( 28472 hom. )

Consequence

TDG
ENST00000544060.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.254

Publications

14 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=-0.8).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.512 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TDG	NM_003211.6 link	c.409-229A>G		intron_variant	Intron 3 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.409-229A>G		intron_variant	Intron 3 of 9	1	NM_003211.6	ENSP00000376611.3		Q13569

Frequencies

GnomAD3 genomes

AF:

0.402

AC:

61121

AN:

152008

Hom.:

14271

Cov.:

show subpopulations

Gnomad AFR

AF:

0.207

Gnomad AMI

AF:

0.543

Gnomad AMR

AF:

0.489

Gnomad ASJ

AF:

0.440

Gnomad EAS

AF:

0.00655

Gnomad SAS

AF:

0.289

Gnomad FIN

AF:

0.520

Gnomad MID

AF:

0.430

Gnomad NFE

AF:

0.516

Gnomad OTH

AF:

0.437

GnomAD4 exome

AF:

0.439

AC:

115194

AN:

262416

Hom.:

28472

Cov.:

AF XY:

0.434

AC XY:

60094

AN XY:

138426

show subpopulations

African (AFR)

AF:

0.195

AC:

1435

AN:

7346

American (AMR)

AF:

0.509

AC:

4554

AN:

8944

Ashkenazi Jewish (ASJ)

AF:

0.447

AC:

3826

AN:

8554

East Asian (EAS)

AF:

0.00602

AC:

116

AN:

19274

South Asian (SAS)

AF:

0.276

AC:

5359

AN:

19422

European-Finnish (FIN)

AF:

0.514

AC:

8157

AN:

15864

Middle Eastern (MID)

AF:

0.417

AC:

493

AN:

1182

European-Non Finnish (NFE)

AF:

0.508

AC:

84416

AN:

166274

Other (OTH)

AF:

0.440

AC:

6838

AN:

15556

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

2818

5637

8455

11274

14092

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

376

752

1128

1504

1880

<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:

0.402

AC:

61124

AN:

152126

Hom.:

14269

Cov.:

AF XY:

0.397

AC XY:

29546

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.206

AC:

8563

AN:

41506

American (AMR)

AF:

0.490

AC:

7481

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.440

AC:

1529

AN:

3472

East Asian (EAS)

AF:

0.00656

AC:

AN:

5180

South Asian (SAS)

AF:

0.287

AC:

1386

AN:

4826

European-Finnish (FIN)

AF:

0.520

AC:

5498

AN:

10568

Middle Eastern (MID)

AF:

0.439

AC:

129

AN:

294

European-Non Finnish (NFE)

AF:

0.516

AC:

35090

AN:

67976

Other (OTH)

AF:

0.435

AC:

919

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1697

3394

5092

6789

8486

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

554

1108

1662

2216

2770

<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:

0.477

Hom.:

29603

Bravo

AF:

0.393

Asia WGS

AF:

0.156

AC:

544

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

(source)

DANN

Benign

0.85

PhyloP100

0.25

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