12-103977072-A-G

Variant names:

• chr12-103977072-A-G
• rs3829300
• NM_003211.6:c.166+12A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003211.6(TDG):​c.166+12A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 1,597,066 control chromosomes in the GnomAD database, including 10,363 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 (841 hom., cov: 33)
  • Exomes 𝑓: 0.11 (9522 hom.)
• Consequence: TDG NM_003211.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20
• Publications: 14 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.295 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TDG	NM_003211.6	MANE Select	c.166+12A>G		intron	N/A	NP_003202.3
	TDG	NM_001363612.2		c.-263-2759A>G		intron	N/A	NP_001350541.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TDG	ENST00000392872.8	TSL:1 MANE Select	c.166+12A>G		intron	N/A	ENSP00000376611.3
	TDG	ENST00000266775.13	TSL:1	c.154+12A>G		intron	N/A	ENSP00000266775.9
	TDG	ENST00000544060.1	TSL:1	n.301+12A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0843 AC: 12828 AN: 152182 Hom.: 841 Cov.: 33

Gnomad AFR AF: 0.0198

Gnomad AMI AF: 0.128

Gnomad AMR AF: 0.100

Gnomad ASJ AF: 0.0646

Gnomad EAS AF: 0.308

Gnomad SAS AF: 0.0925

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.100

Gnomad OTH AF: 0.0798

GnomAD2 exomes AF: 0.113 AC: 26769 AN: 236232 AF XY: 0.110

Gnomad AFR exome AF: 0.0184

Gnomad AMR exome AF: 0.147

Gnomad ASJ exome AF: 0.0641

Gnomad EAS exome AF: 0.298

Gnomad FIN exome AF: 0.100

Gnomad NFE exome AF: 0.102

Gnomad OTH exome AF: 0.0943

GnomAD4 exome AF: 0.106 AC: 153095 AN: 1444766 Hom.: 9522 Cov.: 32 AF XY: 0.106 AC XY: 75806 AN XY: 717978

African (AFR) AF: 0.0143 AC: 461 AN: 32292

American (AMR) AF: 0.139 AC: 5458 AN: 39342

Ashkenazi Jewish (ASJ) AF: 0.0638 AC: 1626 AN: 25502

East Asian (EAS) AF: 0.319 AC: 12620 AN: 39576

South Asian (SAS) AF: 0.0911 AC: 7526 AN: 82620

European-Finnish (FIN) AF: 0.105 AC: 5576 AN: 53330

Middle Eastern (MID) AF: 0.0546 AC: 312 AN: 5712

European-Non Finnish (NFE) AF: 0.102 AC: 113421 AN: 1106622

Other (OTH) AF: 0.102 AC: 6095 AN: 59770

GnomAD4 genome AF: 0.0843 AC: 12832 AN: 152300 Hom.: 841 Cov.: 33 AF XY: 0.0870 AC XY: 6478 AN XY: 74484

African (AFR) AF: 0.0197 AC: 821 AN: 41586

American (AMR) AF: 0.101 AC: 1538 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0646 AC: 224 AN: 3470

East Asian (EAS) AF: 0.308 AC: 1595 AN: 5184

South Asian (SAS) AF: 0.0926 AC: 447 AN: 4828

European-Finnish (FIN) AF: 0.103 AC: 1093 AN: 10614

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.100 AC: 6819 AN: 68008

Other (OTH) AF: 0.0795 AC: 168 AN: 2114

Alfa AF: 0.0984 Hom.: 767

Bravo AF: 0.0828

Asia WGS AF: 0.166 AC: 575 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.031
DANN	Benign	0.78
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3829300; hg19: chr12-104370850; COSMIC: COSV57167932; COSMIC: COSV57167932;