8-124505719-T-G

Position:

• chr8-124505719-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032026.4(TATDN1):​c.517-1372A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.551 in 150,766 control chromosomes in the GnomAD database, including 24,182 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 0.55 (24182 hom., cov: 29)
• Consequence: TATDN1 NM_032026.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05

Genes affected

TATDN1 (HGNC:24220): (TatD DNase domain containing 1) Predicted to enable 3'-5'-exodeoxyribonuclease activity. Predicted to be involved in DNA metabolic process and nucleic acid phosphodiester bond hydrolysis. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.739 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TATDN1	NM_032026.4	c.517-1372A>C		intron_variant		ENST00000276692.11	NP_114415.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TATDN1	ENST00000276692.11	c.517-1372A>C		intron_variant		1	NM_032026.4	ENSP00000276692	P1

Frequencies

GnomAD3 genomes AF: 0.551 AC: 82938 AN: 150648 Hom.: 24132 Cov.: 29

Gnomad AFR AF: 0.745

Gnomad AMI AF: 0.357

Gnomad AMR AF: 0.476

Gnomad ASJ AF: 0.460

Gnomad EAS AF: 0.444

Gnomad SAS AF: 0.531

Gnomad FIN AF: 0.520

Gnomad MID AF: 0.552

Gnomad NFE AF: 0.471

Gnomad OTH AF: 0.530

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

GnomAD4 genome AF: 0.551 AC: 83030 AN: 150766 Hom.: 24182 Cov.: 29 AF XY: 0.550 AC XY: 40441 AN XY: 73566

Gnomad4 AFR AF: 0.746

Gnomad4 AMR AF: 0.475

Gnomad4 ASJ AF: 0.460

Gnomad4 EAS AF: 0.443

Gnomad4 SAS AF: 0.530

Gnomad4 FIN AF: 0.520

Gnomad4 NFE AF: 0.471

Gnomad4 OTH AF: 0.530

Alfa AF: 0.496 Hom.: 9046

Bravo AF: 0.559

Asia WGS AF: 0.519 AC: 1800 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	4.2
DANN	Benign	0.90

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: rs7013683; hg19: chr8-125517960;