dbSNP rs17035056: TDG:c.24-3881G>A (chr12-103973037-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000266775.13(TDG):c.11+4G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0232 in 701,106 control chromosomes in the GnomAD database, including 1,656 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.016 ( 246 hom., cov: 32)

Exomes 𝑓: 0.025 ( 1410 hom. )

Consequence

TDG
ENST00000266775.13 splice_region, intron

Scores

Splicing: ADA: 0.00003497

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.432

Publications

1 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:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript ENST00000266775.13, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.92).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000266775.13. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TDG	NM_003211.6	MANE Select	c.24-3881G>A		intron	N/A	NP_003202.3
	TDG	NM_001363612.2		c.-263-6794G>A		intron	N/A	NP_001350541.1	B4E127

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TDG	ENST00000392872.8	TSL:1 MANE Select	c.24-3881G>A	intron	N/A	ENSP00000376611.3	Q13569
TDG	ENST00000266775.13	TSL:1	c.11+4G>A	splice_region intron	N/A	ENSP00000266775.9	G8JL98
TDG	ENST00000544060.1	TSL:1	n.159-3881G>A	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0164

AC:

2479

AN:

151232

Hom.:

246

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00287

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0432

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.287

Gnomad SAS

AF:

0.0322

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000486

Gnomad OTH

AF:

0.0192

GnomAD2 exomes

AF:

0.0412

AC:

5519

AN:

134090

AF XY:

0.0377

show subpopulations

Gnomad AFR exome

AF:

0.00265

Gnomad AMR exome

AF:

0.0762

Gnomad ASJ exome

AF:

0.000362

Gnomad EAS exome

AF:

0.290

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000417

Gnomad OTH exome

AF:

0.0249

GnomAD4 exome

AF:

0.0251

AC:

13798

AN:

549792

Hom.:

1410

Cov.:

AF XY:

0.0241

AC XY:

7177

AN XY:

297662

show subpopulations

African (AFR)

AF:

0.00285

AC:

AN:

15784

American (AMR)

AF:

0.0729

AC:

2528

AN:

34664

Ashkenazi Jewish (ASJ)

AF:

0.000350

AC:

AN:

19992

East Asian (EAS)

AF:

0.273

AC:

8756

AN:

32022

South Asian (SAS)

AF:

0.0237

AC:

1484

AN:

62720

European-Finnish (FIN)

AF:

0.0000597

AC:

AN:

33486

Middle Eastern (MID)

AF:

0.00148

AC:

AN:

4066

European-Non Finnish (NFE)

AF:

0.000708

AC:

224

AN:

316518

Other (OTH)

AF:

0.0244

AC:

746

AN:

30540

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.449

Heterozygous variant carriers

516

1033

1549

2066

2582

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

132

264

396

528

660

<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:

0.0164

AC:

2485

AN:

151314

Hom.:

246

Cov.:

AF XY:

0.0189

AC XY:

1394

AN XY:

73812

show subpopulations

African (AFR)

AF:

0.00286

AC:

118

AN:

41240

American (AMR)

AF:

0.0437

AC:

663

AN:

15178

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.287

AC:

1475

AN:

5138

South Asian (SAS)

AF:

0.0323

AC:

155

AN:

4800

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10270

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000486

AC:

AN:

67924

Other (OTH)

AF:

0.0196

AC:

AN:

2096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

193

290

386

483

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

144

180

<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:

0.0106

Hom.:

Bravo

AF:

0.0211

Asia WGS

AF:

0.135

AC:

467

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

8.8

(source)

DANN

Benign

0.28

PhyloP100

0.43

Mutation Taster

=92/8

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000035

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over