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

Variant summary

Our verdict is Benign. Variant got -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

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 (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

GnomAD3 exomes

AF:

0.0412

AC:

5519

AN:

134090

Hom.:

535

AF XY:

0.0377

AC XY:

2753

AN XY:

73068

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 SAS exome

AF:

0.0222

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

Gnomad4 AFR exome

AF:

0.00285

Gnomad4 AMR exome

AF:

0.0729

Gnomad4 ASJ exome

AF:

0.000350

Gnomad4 EAS exome

AF:

0.273

Gnomad4 SAS exome

AF:

0.0237

Gnomad4 FIN exome

AF:

0.0000597

Gnomad4 NFE exome

AF:

0.000708

Gnomad4 OTH exome

AF:

0.0244

GnomAD4 genome

AF:

0.0164

AC:

2485

AN:

151314

Hom.:

246

Cov.:

AF XY:

0.0189

AC XY:

1394

AN XY:

73812

show subpopulations

Gnomad4 AFR

AF:

0.00286

Gnomad4 AMR

AF:

0.0437

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.287

Gnomad4 SAS

AF:

0.0323

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000486

Gnomad4 OTH

AF:

0.0196

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

DANN

Benign

0.28

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

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