rs4135054

Variant names:

• chr12-103969832-C-T
• rs4135054
• NM_003211.6:c.23+3772C>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+3772C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 152,036 control chromosomes in the GnomAD database, including 3,112 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 0.18 (3112 hom., cov: 32)
• Consequence: TDG NM_003211.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.544
• Publications: 17 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.328 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TDG	NM_003211.6	c.23+3772C>T		intron_variant	Intron 1 of 9	ENST00000392872.8	NP_003202.3
TDG	NM_001363612.2	c.-264+3772C>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+3772C>T		intron_variant	Intron 1 of 9	1	NM_003211.6	ENSP00000376611.3

Frequencies

GnomAD3 genomes AF: 0.175 AC: 26655 AN: 151920 Hom.: 3110 Cov.: 32

Gnomad AFR AF: 0.333

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.157

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.0939

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.163

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

GnomAD4 genome AF: 0.176 AC: 26692 AN: 152036 Hom.: 3112 Cov.: 32 AF XY: 0.173 AC XY: 12884 AN XY: 74318

African (AFR) AF: 0.333 AC: 13788 AN: 41410

American (AMR) AF: 0.132 AC: 2023 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.161 AC: 558 AN: 3470

East Asian (EAS) AF: 0.157 AC: 812 AN: 5174

South Asian (SAS) AF: 0.115 AC: 554 AN: 4826

European-Finnish (FIN) AF: 0.0939 AC: 993 AN: 10576

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.111 AC: 7534 AN: 67994

Other (OTH) AF: 0.164 AC: 345 AN: 2110

Alfa AF: 0.128 Hom.: 2584

Bravo AF: 0.186

Asia WGS AF: 0.149 AC: 519 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	14
DANN	Benign	0.69
PhyloP100		0.54
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: rs4135054; hg19: chr12-104363610;