rs4135087

chr12-103977447-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003211.6(TDG):c.166+387C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0842 in 152,098 control chromosomes in the GnomAD database, including 836 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 0.084 (836 hom., cov: 32)
• Consequence: TDG NM_003211.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.69

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.294 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TDG	NM_003211.6	c.166+387C>T		intron_variant		ENST00000392872.8
TDG	NM_001363612.2	c.-263-2384C>T		intron_variant
TDG	XM_047429486.1	c.154+387C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TDG	ENST00000392872.8	c.166+387C>T		intron_variant		1	NM_003211.6	P1

Frequencies

GnomAD3 genomes AF: 0.0843 AC: 12808 AN: 151980 Hom.: 836 Cov.: 32

Gnomad AFR AF: 0.0198

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.0646

Gnomad EAS AF: 0.306

Gnomad SAS AF: 0.0927

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.100

Gnomad OTH AF: 0.0793

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

GnomAD4 genome AF: 0.0842 AC: 12812 AN: 152098 Hom.: 836 Cov.: 32 AF XY: 0.0870 AC XY: 6465 AN XY: 74348

Gnomad4 AFR AF: 0.0197

Gnomad4 AMR AF: 0.101

Gnomad4 ASJ AF: 0.0646

Gnomad4 EAS AF: 0.306

Gnomad4 SAS AF: 0.0927

Gnomad4 FIN AF: 0.103

Gnomad4 NFE AF: 0.100

Gnomad4 OTH AF: 0.0789

Alfa AF: 0.0968 Hom.: 256

Bravo AF: 0.0828

Asia WGS AF: 0.166 AC: 575 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	8.7
Dann	Benign	0.69

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

LitVar

Other links and lift over

dbSNP: rs4135087; hg19: chr12-104371225;