Variant rs3751209 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_003211.6(TDG):c.167-9G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 1,539,642 control chromosomes in the GnomAD database, including 51,505 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 0.27 ( 5924 hom., cov: 31)

Exomes 𝑓: 0.25 ( 45581 hom. )

Consequence

TDG
NM_003211.6 intron

Scores

Splicing: ADA: 0.0002368

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.222

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:

TDG (HGNC:):

TDG links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.511 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
TDG	NM_003211.6 linkuse as main transcript	c.167-9G>A	intron_variant	ENST00000392872.8	NP_003202.3	Q13569B4E127
TDG	NM_001363612.2 linkuse as main transcript	c.-263-9G>A	intron_variant		NP_001350541.1
TDG	XM_047429486.1 linkuse as main transcript	c.155-9G>A	intron_variant		XP_047285442.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TDG	ENST00000392872.8 linkuse as main transcript	c.167-9G>A		intron_variant		1	NM_003211.6	ENSP00000376611.3		Q13569

Frequencies

GnomAD3 genomes

AF:

0.271

AC:

40912

AN:

150842

Hom.:

5917

Cov.:

show subpopulations

Gnomad AFR

AF:

0.305

Gnomad AMI

AF:

0.209

Gnomad AMR

AF:

0.224

Gnomad ASJ

AF:

0.283

Gnomad EAS

AF:

0.528

Gnomad SAS

AF:

0.409

Gnomad FIN

AF:

0.289

Gnomad MID

AF:

0.256

Gnomad NFE

AF:

0.231

Gnomad OTH

AF:

0.242

GnomAD3 exomes

AF:

0.282

AC:

55092

AN:

195484

Hom.:

8680

AF XY:

0.285

AC XY:

30339

AN XY:

106474

show subpopulations

Gnomad AFR exome

AF:

0.305

Gnomad AMR exome

AF:

0.207

Gnomad ASJ exome

AF:

0.279

Gnomad EAS exome

AF:

0.544

Gnomad SAS exome

AF:

0.413

Gnomad FIN exome

AF:

0.275

Gnomad NFE exome

AF:

0.227

Gnomad OTH exome

AF:

0.254

GnomAD4 exome

AF:

0.248

AC:

344439

AN:

1388682

Hom.:

45581

Cov.:

AF XY:

0.252

AC XY:

173322

AN XY:

686532

show subpopulations

Gnomad4 AFR exome

AF:

0.307

Gnomad4 AMR exome

AF:

0.216

Gnomad4 ASJ exome

AF:

0.281

Gnomad4 EAS exome

AF:

0.496

Gnomad4 SAS exome

AF:

0.414

Gnomad4 FIN exome

AF:

0.272

Gnomad4 NFE exome

AF:

0.224

Gnomad4 OTH exome

AF:

0.269

GnomAD4 genome

AF:

0.271

AC:

40945

AN:

150960

Hom.:

5924

Cov.:

AF XY:

0.278

AC XY:

20459

AN XY:

73688

show subpopulations

Gnomad4 AFR

AF:

0.305

Gnomad4 AMR

AF:

0.223

Gnomad4 ASJ

AF:

0.283

Gnomad4 EAS

AF:

0.528

Gnomad4 SAS

AF:

0.411

Gnomad4 FIN

AF:

0.289

Gnomad4 NFE

AF:

0.231

Gnomad4 OTH

AF:

0.246

Alfa

AF:

0.241

Hom.:

8192

Bravo

AF:

0.263

Asia WGS

AF:

0.473

AC:

1644

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Benign

0.73

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00024

dbscSNV1_RF

Benign

0.012

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

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