rs4135106

Positions:

• chr12-103982060-T-C

Variant summary

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

The ENST00000392872.8(TDG):​c.479-739T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0515 in 152,252 control chromosomes in the GnomAD database, including 276 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 0.052 (276 hom., cov: 31)
• Consequence: TDG ENST00000392872.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.377

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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0719 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TDG	NM_003211.6	c.479-739T>C		intron_variant		ENST00000392872.8	NP_003202.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TDG	ENST00000392872.8	c.479-739T>C		intron_variant		1	NM_003211.6	ENSP00000376611	P1

Frequencies

GnomAD3 genomes AF: 0.0516 AC: 7847 AN: 152134 Hom.: 276 Cov.: 31

Gnomad AFR AF: 0.0133

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0472

Gnomad ASJ AF: 0.0773

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0188

Gnomad FIN AF: 0.0995

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0736

Gnomad OTH AF: 0.0617

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

GnomAD4 genome AF: 0.0515 AC: 7845 AN: 152252 Hom.: 276 Cov.: 31 AF XY: 0.0520 AC XY: 3870 AN XY: 74444

Gnomad4 AFR AF: 0.0133

Gnomad4 AMR AF: 0.0471

Gnomad4 ASJ AF: 0.0773

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0186

Gnomad4 FIN AF: 0.0995

Gnomad4 NFE AF: 0.0736

Gnomad4 OTH AF: 0.0605

Alfa AF: 0.0648 Hom.: 265

Bravo AF: 0.0471

Asia WGS AF: 0.00693 AC: 24 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.73
DANN	Benign	0.43

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: rs4135106; hg19: chr12-104375838;