12-103975348-T-C

Variant names:

• chr12-103975348-T-C
• rs2723877
• NM_003211.6:c.24-1570T>C

Variant summary

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

The NM_003211.6(TDG):​c.24-1570T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.9 in 152,250 control chromosomes in the GnomAD database, including 61,690 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 0.90 (61690 hom., cov: 33)
• Consequence: TDG NM_003211.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.638
• Publications: 4 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TDG	NM_003211.6	c.24-1570T>C		intron_variant	Intron 1 of 9	ENST00000392872.8	NP_003202.3
TDG	NM_001363612.2	c.-263-4483T>C		intron_variant	Intron 1 of 8		NP_001350541.1
TDG	XM_047429486.1	c.12-1570T>C		intron_variant	Intron 1 of 9		XP_047285442.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TDG	ENST00000392872.8	c.24-1570T>C		intron_variant	Intron 1 of 9	1	NM_003211.6	ENSP00000376611.3

Frequencies

GnomAD3 genomes AF: 0.900 AC: 136855 AN: 152132 Hom.: 61650 Cov.: 33

Gnomad AFR AF: 0.883

Gnomad AMI AF: 0.904

Gnomad AMR AF: 0.921

Gnomad ASJ AF: 0.909

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.917

Gnomad FIN AF: 0.938

Gnomad MID AF: 0.880

Gnomad NFE AF: 0.890

Gnomad OTH AF: 0.897

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

GnomAD4 genome AF: 0.900 AC: 136955 AN: 152250 Hom.: 61690 Cov.: 33 AF XY: 0.903 AC XY: 67218 AN XY: 74430

African (AFR) AF: 0.883 AC: 36668 AN: 41512

American (AMR) AF: 0.921 AC: 14095 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.909 AC: 3155 AN: 3472

East Asian (EAS) AF: 0.998 AC: 5176 AN: 5184

South Asian (SAS) AF: 0.916 AC: 4428 AN: 4832

European-Finnish (FIN) AF: 0.938 AC: 9939 AN: 10596

Middle Eastern (MID) AF: 0.878 AC: 258 AN: 294

European-Non Finnish (NFE) AF: 0.890 AC: 60518 AN: 68030

Other (OTH) AF: 0.897 AC: 1897 AN: 2114

Alfa AF: 0.903 Hom.: 10804

Bravo AF: 0.898

Asia WGS AF: 0.950 AC: 3303 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.0
DANN	Benign	0.44
PhyloP100		-0.64
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: rs2723877; hg19: chr12-104369126;