12-103968698-A-T

Variant names:

• chr12-103968698-A-T
• rs4135050
• NM_003211.6:c.23+2638A>T

Variant summary

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

The NM_003211.6(TDG):​c.23+2638A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.761 in 152,222 control chromosomes in the GnomAD database, including 44,401 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 0.76 (44401 hom., cov: 33)
• Consequence: TDG NM_003211.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.415
• Publications: 5 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TDG	NM_003211.6	c.23+2638A>T		intron_variant	Intron 1 of 9	ENST00000392872.8	NP_003202.3
TDG	NM_001363612.2	c.-264+2638A>T		intron_variant	Intron 1 of 8		NP_001350541.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TDG	ENST00000392872.8	c.23+2638A>T		intron_variant	Intron 1 of 9	1	NM_003211.6	ENSP00000376611.3

Frequencies

GnomAD3 genomes AF: 0.761 AC: 115823 AN: 152104 Hom.: 44372 Cov.: 33

Gnomad AFR AF: 0.762

Gnomad AMI AF: 0.632

Gnomad AMR AF: 0.722

Gnomad ASJ AF: 0.719

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.847

Gnomad FIN AF: 0.847

Gnomad MID AF: 0.693

Gnomad NFE AF: 0.737

Gnomad OTH AF: 0.752

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

GnomAD4 genome AF: 0.761 AC: 115904 AN: 152222 Hom.: 44401 Cov.: 33 AF XY: 0.770 AC XY: 57317 AN XY: 74434

African (AFR) AF: 0.762 AC: 31636 AN: 41520

American (AMR) AF: 0.721 AC: 11034 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.719 AC: 2494 AN: 3468

East Asian (EAS) AF: 0.997 AC: 5169 AN: 5186

South Asian (SAS) AF: 0.846 AC: 4085 AN: 4828

European-Finnish (FIN) AF: 0.847 AC: 8968 AN: 10588

Middle Eastern (MID) AF: 0.690 AC: 203 AN: 294

European-Non Finnish (NFE) AF: 0.737 AC: 50151 AN: 68016

Other (OTH) AF: 0.752 AC: 1588 AN: 2112

Alfa AF: 0.755 Hom.: 5397

Bravo AF: 0.751

Asia WGS AF: 0.903 AC: 3139 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	4.4
DANN	Benign	0.72
PhyloP100		0.41
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: rs4135050; hg19: chr12-104362476;