rs4135081

Variant names:

• chr12-103975268-A-G
• rs4135081
• NM_003211.6:c.24-1650A>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.24-1650A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 152,126 control chromosomes in the GnomAD database, including 7,971 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 0.30 (7971 hom., cov: 33)
• Consequence: TDG NM_003211.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.196
• Publications: 8 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.379 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.24-1650A>G		intron	N/A	NP_003202.3
	TDG	NM_001363612.2		c.-263-4563A>G		intron	N/A	NP_001350541.1	B4E127

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TDG	ENST00000392872.8	TSL:1 MANE Select	c.24-1650A>G		intron	N/A	ENSP00000376611.3	Q13569
	TDG	ENST00000266775.13	TSL:1	c.12-1650A>G		intron	N/A	ENSP00000266775.9	G8JL98
	TDG	ENST00000544060.1	TSL:1	n.159-1650A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.301 AC: 45781 AN: 152008 Hom.: 7977 Cov.: 33

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.295

Gnomad AMR AF: 0.312

Gnomad ASJ AF: 0.301

Gnomad EAS AF: 0.00808

Gnomad SAS AF: 0.317

Gnomad FIN AF: 0.414

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.383

Gnomad OTH AF: 0.333

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

GnomAD4 genome AF: 0.301 AC: 45783 AN: 152126 Hom.: 7971 Cov.: 33 AF XY: 0.300 AC XY: 22333 AN XY: 74356

African (AFR) AF: 0.168 AC: 6966 AN: 41526

American (AMR) AF: 0.312 AC: 4770 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.301 AC: 1044 AN: 3472

East Asian (EAS) AF: 0.00829 AC: 43 AN: 5186

South Asian (SAS) AF: 0.315 AC: 1516 AN: 4820

European-Finnish (FIN) AF: 0.414 AC: 4375 AN: 10556

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.383 AC: 26024 AN: 67970

Other (OTH) AF: 0.330 AC: 695 AN: 2106

Alfa AF: 0.333 Hom.: 1590

Bravo AF: 0.286

Asia WGS AF: 0.170 AC: 592 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	12
DANN	Benign	0.62
PhyloP100		0.20
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4135081; hg19: chr12-104369046;