12-103980664-A-G

Variant names:

• chr12-103980664-A-G
• rs1866074
• ENST00000544060.1:n.1135A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000544060.1(TDG):​n.1135A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.425 in 414,542 control chromosomes in the GnomAD database, including 42,741 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 0.40 (14269 hom., cov: 32)
  • Exomes 𝑓: 0.44 (28472 hom.)
• Consequence: TDG ENST00000544060.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.254
• Publications: 14 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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.512 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000544060.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TDG	NM_003211.6	MANE Select	c.409-229A>G		intron	N/A	NP_003202.3
	TDG	NM_001363612.2		c.-21-229A>G		intron	N/A	NP_001350541.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TDG	ENST00000544060.1	TSL:1	n.1135A>G		non_coding_transcript_exon	Exon 3 of 3
	TDG	ENST00000392872.8	TSL:1 MANE Select	c.409-229A>G		intron	N/A	ENSP00000376611.3
	TDG	ENST00000266775.13	TSL:1	c.397-229A>G		intron	N/A	ENSP00000266775.9

Frequencies

GnomAD3 genomes AF: 0.402 AC: 61121 AN: 152008 Hom.: 14271 Cov.: 32

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.543

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.440

Gnomad EAS AF: 0.00655

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.520

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.516

Gnomad OTH AF: 0.437

GnomAD4 exome AF: 0.439 AC: 115194 AN: 262416 Hom.: 28472 Cov.: 4 AF XY: 0.434 AC XY: 60094 AN XY: 138426

African (AFR) AF: 0.195 AC: 1435 AN: 7346

American (AMR) AF: 0.509 AC: 4554 AN: 8944

Ashkenazi Jewish (ASJ) AF: 0.447 AC: 3826 AN: 8554

East Asian (EAS) AF: 0.00602 AC: 116 AN: 19274

South Asian (SAS) AF: 0.276 AC: 5359 AN: 19422

European-Finnish (FIN) AF: 0.514 AC: 8157 AN: 15864

Middle Eastern (MID) AF: 0.417 AC: 493 AN: 1182

European-Non Finnish (NFE) AF: 0.508 AC: 84416 AN: 166274

Other (OTH) AF: 0.440 AC: 6838 AN: 15556

GnomAD4 genome AF: 0.402 AC: 61124 AN: 152126 Hom.: 14269 Cov.: 32 AF XY: 0.397 AC XY: 29546 AN XY: 74360

African (AFR) AF: 0.206 AC: 8563 AN: 41506

American (AMR) AF: 0.490 AC: 7481 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.440 AC: 1529 AN: 3472

East Asian (EAS) AF: 0.00656 AC: 34 AN: 5180

South Asian (SAS) AF: 0.287 AC: 1386 AN: 4826

European-Finnish (FIN) AF: 0.520 AC: 5498 AN: 10568

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.516 AC: 35090 AN: 67976

Other (OTH) AF: 0.435 AC: 919 AN: 2114

Alfa AF: 0.477 Hom.: 29603

Bravo AF: 0.393

Asia WGS AF: 0.156 AC: 544 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	10
DANN	Benign	0.85
PhyloP100		0.25
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: rs1866074; hg19: chr12-104374442;