rs4135061

Variant names:

• chr12-103971733-G-A
• rs4135061
• NM_003211.6:c.24-5185G>A

Your query was ambiguous. Multiple possible variants found:

• chr12-103971733-G-A
• chr12-103971733-G-C
• chr12-103971733-G-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.24-5185G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.765 in 152,112 control chromosomes in the GnomAD database, including 44,797 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 0.77 (44797 hom., cov: 32)
• Consequence: TDG NM_003211.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.233
• Publications: 0 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.

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.24-5185G>A		intron	N/A	NP_003202.3
	TDG	NM_001363612.2		c.-264+5673G>A		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.24-5185G>A		intron	N/A	ENSP00000376611.3	Q13569
	TDG	ENST00000266775.13	TSL:1	c.-63-1227G>A		intron	N/A	ENSP00000266775.9	G8JL98
	TDG	ENST00000544060.1	TSL:1	n.159-5185G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.765 AC: 116317 AN: 151996 Hom.: 44769 Cov.: 32

Gnomad AFR AF: 0.773

Gnomad AMI AF: 0.632

Gnomad AMR AF: 0.724

Gnomad ASJ AF: 0.719

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.847

Gnomad FIN AF: 0.846

Gnomad MID AF: 0.697

Gnomad NFE AF: 0.738

Gnomad OTH AF: 0.755

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

GnomAD4 genome AF: 0.765 AC: 116399 AN: 152112 Hom.: 44797 Cov.: 32 AF XY: 0.774 AC XY: 57526 AN XY: 74356

African (AFR) AF: 0.773 AC: 32082 AN: 41488

American (AMR) AF: 0.724 AC: 11058 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.719 AC: 2493 AN: 3468

East Asian (EAS) AF: 0.997 AC: 5173 AN: 5190

South Asian (SAS) AF: 0.847 AC: 4078 AN: 4816

European-Finnish (FIN) AF: 0.846 AC: 8947 AN: 10572

Middle Eastern (MID) AF: 0.695 AC: 203 AN: 292

European-Non Finnish (NFE) AF: 0.738 AC: 50197 AN: 67986

Other (OTH) AF: 0.755 AC: 1593 AN: 2110

Alfa AF: 0.699 Hom.: 2311

Bravo AF: 0.755

Asia WGS AF: 0.903 AC: 3139 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.1
DANN	Benign	0.70
PhyloP100		-0.23
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs4135061;

hg19: chr12-104365511;