12-103985728-A-ATTGAGAGC

Position:

• chr12-103985728-A-ATTGAGAGC

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_003211.6(TDG):​c.1090_1090+1insTTGAGAGC​(p.Val367LeufsTer6) variant causes a frameshift, splice region change. Variant has been reported in ClinVar as Uncertain significance (★). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.0087 (0 hom., cov: 22)
  • Exomes 𝑓: 0.047 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TDG NM_003211.6 frameshift, splice_region
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.93

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 Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TDG	NM_003211.6	c.1090_1090+1insTTGAGAGC	p.Val367LeufsTer6	frameshift_variant, splice_region_variant		ENST00000392872.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TDG	ENST00000392872.8	c.1090_1090+1insTTGAGAGC	p.Val367LeufsTer6	frameshift_variant, splice_region_variant		1	NM_003211.6	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 1208 AN: 138494 Hom.: 0 Cov.: 22 FAILED QC

Gnomad AFR AF: 0.0120

Gnomad AMI AF: 0.0131

Gnomad AMR AF: 0.0107

Gnomad ASJ AF: 0.00650

Gnomad EAS AF: 0.00962

Gnomad SAS AF: 0.0120

Gnomad FIN AF: 0.0114

Gnomad MID AF: 0.0179

Gnomad NFE AF: 0.00557

Gnomad OTH AF: 0.0115

GnomAD3 exomes AF: 0.0125 AC: 2996 AN: 240478 Hom.: 0 AF XY: 0.0139 AC XY: 1804 AN XY: 129948

Gnomad AFR exome AF: 0.00558

Gnomad AMR exome AF: 0.0114

Gnomad ASJ exome AF: 0.0313

Gnomad EAS exome AF: 0.00512

Gnomad SAS exome AF: 0.0265

Gnomad FIN exome AF: 0.00910

Gnomad NFE exome AF: 0.0102

Gnomad OTH exome AF: 0.0143

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0475 AC: 60691 AN: 1278396 Hom.: 0 Cov.: 34 AF XY: 0.0493 AC XY: 31437 AN XY: 638078

Gnomad4 AFR exome AF: 0.0780

Gnomad4 AMR exome AF: 0.0858

Gnomad4 ASJ exome AF: 0.0928

Gnomad4 EAS exome AF: 0.113

Gnomad4 SAS exome AF: 0.0684

Gnomad4 FIN exome AF: 0.0798

Gnomad4 NFE exome AF: 0.0375

Gnomad4 OTH exome AF: 0.0595

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00872 AC: 1209 AN: 138594 Hom.: 0 Cov.: 22 AF XY: 0.00895 AC XY: 606 AN XY: 67710

Gnomad4 AFR AF: 0.0120

Gnomad4 AMR AF: 0.0107

Gnomad4 ASJ AF: 0.00650

Gnomad4 EAS AF: 0.00965

Gnomad4 SAS AF: 0.0116

Gnomad4 FIN AF: 0.0114

Gnomad4 NFE AF: 0.00557

Gnomad4 OTH AF: 0.0114

Alfa AF: 0.0447 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Hereditary breast ovarian cancer syndrome Uncertain:1

Uncertain significance, criteria provided, single submitter

research

Molecular Oncology Research Center, Barretos Cancer Hospital

Aug 01, 2020

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs765686214; hg19: chr12-104379506;