rs1866074

chr12-103980664-A-Gchr12-103980664-A-T

Variant summary

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

The NM_003211.6(TDG):c.409-229A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.425 in 414,542 control chromosomes in the GnomAD database, including 42,741 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 0.40 (14269 hom., cov: 32)
  • Exomes 𝑓: 0.44 (28472 hom.)
• Consequence: TDG NM_003211.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.254

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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.512 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TDG	NM_003211.6	c.409-229A>G		intron_variant		ENST00000392872.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TDG	ENST00000392872.8	c.409-229A>G		intron_variant		1	NM_003211.6	P1

Frequencies

GnomAD3 genomes AF: 0.402 AC: 61121 AN: 152008 Hom.: 14271 Cov.: 32

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.543

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.440

Gnomad EAS AF: 0.00655

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.520

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.516

Gnomad OTH AF: 0.437

GnomAD4 exome AF: 0.439 AC: 115194 AN: 262416 Hom.: 28472 Cov.: 4 AF XY: 0.434 AC XY: 60094 AN XY: 138426

Gnomad4 AFR exome AF: 0.195

Gnomad4 AMR exome AF: 0.509

Gnomad4 ASJ exome AF: 0.447

Gnomad4 EAS exome AF: 0.00602

Gnomad4 SAS exome AF: 0.276

Gnomad4 FIN exome AF: 0.514

Gnomad4 NFE exome AF: 0.508

Gnomad4 OTH exome AF: 0.440

GnomAD4 genome AF: 0.402 AC: 61124 AN: 152126 Hom.: 14269 Cov.: 32 AF XY: 0.397 AC XY: 29546 AN XY: 74360

Gnomad4 AFR AF: 0.206

Gnomad4 AMR AF: 0.490

Gnomad4 ASJ AF: 0.440

Gnomad4 EAS AF: 0.00656

Gnomad4 SAS AF: 0.287

Gnomad4 FIN AF: 0.520

Gnomad4 NFE AF: 0.516

Gnomad4 OTH AF: 0.435

Alfa AF: 0.482 Hom.: 23589

Bravo AF: 0.393

Asia WGS AF: 0.156 AC: 544 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	10
Dann	Benign	0.85

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: rs1866074; hg19: chr12-104374442;