dbSNP rs167715: TDG:c.166+529G>A (chr12-103977589-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.166+529G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.9 in 152,292 control chromosomes in the GnomAD database, including 61,705 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 0.90 ( 61705 hom., cov: 32)

Consequence

TDG
NM_003211.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.58

Publications

5 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003211.6. 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.166+529G>A		intron	N/A	NP_003202.3
	TDG	NM_001363612.2		c.-263-2242G>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.166+529G>A	intron	N/A	ENSP00000376611.3	Q13569
TDG	ENST00000266775.13	TSL:1	c.154+529G>A	intron	N/A	ENSP00000266775.9	G8JL98
TDG	ENST00000544060.1	TSL:1	n.301+529G>A	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.900

AC:

136894

AN:

152174

Hom.:

61665

Cov.:

show subpopulations

Gnomad AFR

AF:

0.883

Gnomad AMI

AF:

0.902

Gnomad AMR

AF:

0.921

Gnomad ASJ

AF:

0.909

Gnomad EAS

AF:

0.998

Gnomad SAS

AF:

0.917

Gnomad FIN

AF:

0.938

Gnomad MID

AF:

0.885

Gnomad NFE

AF:

0.890

Gnomad OTH

AF:

0.896

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.900

AC:

136994

AN:

152292

Hom.:

61705

Cov.:

AF XY:

0.903

AC XY:

67254

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.883

AC:

36690

AN:

41540

American (AMR)

AF:

0.921

AC:

14097

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.909

AC:

3155

AN:

3472

East Asian (EAS)

AF:

0.998

AC:

5182

AN:

5190

South Asian (SAS)

AF:

0.916

AC:

4426

AN:

4830

European-Finnish (FIN)

AF:

0.938

AC:

9959

AN:

10614

Middle Eastern (MID)

AF:

0.884

AC:

258

AN:

292

European-Non Finnish (NFE)

AF:

0.890

AC:

60510

AN:

68020

Other (OTH)

AF:

0.897

AC:

1894

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

725

1449

2174

2898

3623

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

900

1800

2700

3600

4500

<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:

0.892

Hom.:

118470

Bravo

AF:

0.898

Asia WGS

AF:

0.951

AC:

3304

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.037

(source)

DANN

Benign

0.35

PhyloP100

-1.6

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over