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 NM_003211.6(TDG):c.24-3881G>A variant causes a 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. 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
NM_003211.6 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

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
TDG	NM_003211.6 link	c.24-3881G>A	intron_variant	Intron 1 of 9	ENST00000392872.8	NP_003202.3	Q13569B4E127
TDG	NM_001363612.2 link	c.-263-6794G>A	intron_variant	Intron 1 of 8		NP_001350541.1
TDG	XM_047429486.1 link	c.11+4G>A	splice_region_variant, intron_variant	Intron 1 of 9		XP_047285442.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TDG	ENST00000392872.8 link	c.24-3881G>A		intron_variant	Intron 1 of 9	1	NM_003211.6	ENSP00000376611.3		Q13569

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 v4.3

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

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