chr12-103975268-A-G

Position:

• chr12-103975268-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TDG	NM_003211.6	c.24-1650A>G		intron_variant		ENST00000392872.8
TDG	NM_001363612.2	c.-263-4563A>G		intron_variant
TDG	XM_047429486.1	c.12-1650A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TDG	ENST00000392872.8	c.24-1650A>G		intron_variant		1	NM_003211.6	P1

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

Gnomad4 AFR AF: 0.168

Gnomad4 AMR AF: 0.312

Gnomad4 ASJ AF: 0.301

Gnomad4 EAS AF: 0.00829

Gnomad4 SAS AF: 0.315

Gnomad4 FIN AF: 0.414

Gnomad4 NFE AF: 0.383

Gnomad4 OTH AF: 0.330

Alfa AF: 0.338 Hom.: 1584

Bravo AF: 0.286

Asia WGS AF: 0.170 AC: 592 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	12
DANN	Benign	0.62

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

Publications

LitVar

Other links and lift over

dbSNP: rs4135081; hg19: chr12-104369046;