12-103978878-A-G

Variant names:

• chr12-103978878-A-G
• rs10861152
• NM_003211.6:c.167-953A>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.167-953A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.604 in 151,760 control chromosomes in the GnomAD database, including 27,975 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 0.60 (27975 hom., cov: 29)
• Consequence: TDG NM_003211.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.991
• Publications: 11 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.707 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TDG	NM_003211.6	c.167-953A>G		intron_variant	Intron 2 of 9	ENST00000392872.8	NP_003202.3
TDG	NM_001363612.2	c.-263-953A>G		intron_variant	Intron 1 of 8		NP_001350541.1
TDG	XM_047429486.1	c.155-953A>G		intron_variant	Intron 2 of 9		XP_047285442.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TDG	ENST00000392872.8	c.167-953A>G		intron_variant	Intron 2 of 9	1	NM_003211.6	ENSP00000376611.3

Frequencies

GnomAD3 genomes AF: 0.604 AC: 91624 AN: 151640 Hom.: 27961 Cov.: 29

Gnomad AFR AF: 0.569

Gnomad AMI AF: 0.502

Gnomad AMR AF: 0.553

Gnomad ASJ AF: 0.585

Gnomad EAS AF: 0.535

Gnomad SAS AF: 0.728

Gnomad FIN AF: 0.725

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.618

Gnomad OTH AF: 0.589

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

GnomAD4 genome AF: 0.604 AC: 91684 AN: 151760 Hom.: 27975 Cov.: 29 AF XY: 0.610 AC XY: 45206 AN XY: 74158

African (AFR) AF: 0.569 AC: 23516 AN: 41326

American (AMR) AF: 0.553 AC: 8429 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.585 AC: 2030 AN: 3470

East Asian (EAS) AF: 0.535 AC: 2754 AN: 5144

South Asian (SAS) AF: 0.727 AC: 3495 AN: 4808

European-Finnish (FIN) AF: 0.725 AC: 7631 AN: 10520

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.618 AC: 41973 AN: 67930

Other (OTH) AF: 0.590 AC: 1240 AN: 2102

Alfa AF: 0.606 Hom.: 45954

Bravo AF: 0.586

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.7
DANN	Benign	0.62
PhyloP100		0.99
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: rs10861152; hg19: chr12-104372656;