12-103979822-G-A

Variant names:

• chr12-103979822-G-A
• rs3751209
• NM_003211.6:c.167-9G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_003211.6(TDG):​c.167-9G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 1,539,642 control chromosomes in the GnomAD database, including 51,505 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 0.27 (5924 hom., cov: 31)
  • Exomes 𝑓: 0.25 (45581 hom.)
• Consequence: TDG NM_003211.6 intron
• Scores: Splicing: ADA: 0.0002368
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.222
• Publications: 20 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.511 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TDG	NM_003211.6	c.167-9G>A		intron_variant	Intron 2 of 9	ENST00000392872.8	NP_003202.3
TDG	NM_001363612.2	c.-263-9G>A		intron_variant	Intron 1 of 8		NP_001350541.1
TDG	XM_047429486.1	c.155-9G>A		intron_variant	Intron 2 of 9		XP_047285442.1
TDG	XM_047429488.1	c.-422G>A		upstream_gene_variant			XP_047285444.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.271 AC: 40912 AN: 150842 Hom.: 5917 Cov.: 31

Gnomad AFR AF: 0.305

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.283

Gnomad EAS AF: 0.528

Gnomad SAS AF: 0.409

Gnomad FIN AF: 0.289

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.231

Gnomad OTH AF: 0.242

GnomAD2 exomes AF: 0.282 AC: 55092 AN: 195484 AF XY: 0.285

Gnomad AFR exome AF: 0.305

Gnomad AMR exome AF: 0.207

Gnomad ASJ exome AF: 0.279

Gnomad EAS exome AF: 0.544

Gnomad FIN exome AF: 0.275

Gnomad NFE exome AF: 0.227

Gnomad OTH exome AF: 0.254

GnomAD4 exome AF: 0.248 AC: 344439 AN: 1388682 Hom.: 45581 Cov.: 31 AF XY: 0.252 AC XY: 173322 AN XY: 686532

African (AFR) AF: 0.307 AC: 9251 AN: 30092

American (AMR) AF: 0.216 AC: 6008 AN: 27854

Ashkenazi Jewish (ASJ) AF: 0.281 AC: 6131 AN: 21798

East Asian (EAS) AF: 0.496 AC: 19246 AN: 38768

South Asian (SAS) AF: 0.414 AC: 30253 AN: 73050

European-Finnish (FIN) AF: 0.272 AC: 13774 AN: 50684

Middle Eastern (MID) AF: 0.333 AC: 1773 AN: 5330

European-Non Finnish (NFE) AF: 0.224 AC: 242664 AN: 1084038

Other (OTH) AF: 0.269 AC: 15339 AN: 57068

GnomAD4 genome AF: 0.271 AC: 40945 AN: 150960 Hom.: 5924 Cov.: 31 AF XY: 0.278 AC XY: 20459 AN XY: 73688

African (AFR) AF: 0.305 AC: 12502 AN: 41042

American (AMR) AF: 0.223 AC: 3377 AN: 15126

Ashkenazi Jewish (ASJ) AF: 0.283 AC: 981 AN: 3464

East Asian (EAS) AF: 0.528 AC: 2724 AN: 5160

South Asian (SAS) AF: 0.411 AC: 1964 AN: 4780

European-Finnish (FIN) AF: 0.289 AC: 3004 AN: 10378

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.231 AC: 15617 AN: 67726

Other (OTH) AF: 0.246 AC: 514 AN: 2086

Alfa AF: 0.244 Hom.: 18992

Bravo AF: 0.263

Asia WGS AF: 0.473 AC: 1644 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	17
DANN	Benign	0.73
PhyloP100		0.22
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00024
dbscSNV1_RF	Benign	0.012
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: rs3751209; hg19: chr12-104373600; COSMIC: COSV57165052; COSMIC: COSV57165052;