Genetic Variant NM_003211.6:c.167-9G>A (chr12-103979822-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -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

Publications

20 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 -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	Exon rank	MANE	Protein	UniProt
TDG	NM_003211.6 link	c.167-9G>A	intron_variant	Intron 2 of 9	ENST00000392872.8	NP_003202.3	Q13569B4E127
TDG	NM_001363612.2 link	c.-263-9G>A	intron_variant	Intron 1 of 8		NP_001350541.1
TDG	XM_047429486.1 link	c.155-9G>A	intron_variant	Intron 2 of 9		XP_047285442.1
TDG	XM_047429488.1 link	c.-422G>A	upstream_gene_variant			XP_047285444.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TDG	ENST00000392872.8 link	c.167-9G>A		intron_variant	Intron 2 of 9	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

GnomAD2 exomes

AF:

0.282

AC:

55092

AN:

195484

AF XY:

0.285

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 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

African (AFR)

AF:

0.307

AC:

9251

AN:

30092

American (AMR)

AF:

0.216

AC:

6008

AN:

27854

Ashkenazi Jewish (ASJ)

AF:

0.281

AC:

6131

AN:

21798

East Asian (EAS)

AF:

0.496

AC:

19246

AN:

38768

South Asian (SAS)

AF:

0.414

AC:

30253

AN:

73050

European-Finnish (FIN)

AF:

0.272

AC:

13774

AN:

50684

Middle Eastern (MID)

AF:

0.333

AC:

1773

AN:

5330

European-Non Finnish (NFE)

AF:

0.224

AC:

242664

AN:

1084038

Other (OTH)

AF:

0.269

AC:

15339

AN:

57068

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

12023

24047

36070

48094

60117

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8812

17624

26436

35248

44060

<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:

0.271

AC:

40945

AN:

150960

Hom.:

5924

Cov.:

AF XY:

0.278

AC XY:

20459

AN XY:

73688

show subpopulations

African (AFR)

AF:

0.305

AC:

12502

AN:

41042

American (AMR)

AF:

0.223

AC:

3377

AN:

15126

Ashkenazi Jewish (ASJ)

AF:

0.283

AC:

981

AN:

3464

East Asian (EAS)

AF:

0.528

AC:

2724

AN:

5160

South Asian (SAS)

AF:

0.411

AC:

1964

AN:

4780

European-Finnish (FIN)

AF:

0.289

AC:

3004

AN:

10378

Middle Eastern (MID)

AF:

0.248

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.231

AC:

15617

AN:

67726

Other (OTH)

AF:

0.246

AC:

514

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1459

2918

4376

5835

7294

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

432

864

1296

1728

2160

<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:

0.244

Hom.:

18992

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

(source)

DANN

Benign

0.73

PhyloP100

0.22

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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