rs12548836

Positions:

• chr8-124517114-G-A

Variant summary

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

The NM_032026.4(TATDN1):​c.203-1084C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 152,240 control chromosomes in the GnomAD database, including 2,275 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 0.15 (2275 hom., cov: 32)
• Consequence: TATDN1 NM_032026.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.221

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TATDN1	NM_032026.4	c.203-1084C>T		intron_variant		ENST00000276692.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TATDN1	ENST00000276692.11	c.203-1084C>T		intron_variant		1	NM_032026.4	P1

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23391 AN: 152124 Hom.: 2273 Cov.: 32

Gnomad AFR AF: 0.0421

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.0879

Gnomad SAS AF: 0.0926

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.182

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

GnomAD4 genome AF: 0.154 AC: 23392 AN: 152240 Hom.: 2275 Cov.: 32 AF XY: 0.150 AC XY: 11189 AN XY: 74456

Gnomad4 AFR AF: 0.0420

Gnomad4 AMR AF: 0.244

Gnomad4 ASJ AF: 0.169

Gnomad4 EAS AF: 0.0883

Gnomad4 SAS AF: 0.0928

Gnomad4 FIN AF: 0.170

Gnomad4 NFE AF: 0.206

Gnomad4 OTH AF: 0.183

Alfa AF: 0.188 Hom.: 1348

Bravo AF: 0.162

Asia WGS AF: 0.111 AC: 383 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	0.48
DANN	Benign	0.34

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: rs12548836; hg19: chr8-125529355;