8-9743407-T-C

Position:

• chr8-9743407-T-C

Variant summary

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

The NM_003747.3(TNKS):​c.2644-4617T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 152,192 control chromosomes in the GnomAD database, including 3,146 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 0.18 (3146 hom., cov: 32)
  • Exomes 𝑓: 0.25 (0 hom.)
• Consequence: TNKS NM_003747.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.914

Genes affected

TNKS (HGNC:11941): (tankyrase) Enables histone binding activity; pentosyltransferase activity; and zinc ion binding activity. Involved in several processes, including negative regulation of maintenance of mitotic sister chromatid cohesion, telomeric; protein ADP-ribosylation; and regulation of nucleobase-containing compound metabolic process. Acts upstream of or within peptidyl-serine phosphorylation; peptidyl-threonine phosphorylation; and protein ADP-ribosylation. Located in several cellular components, including chromosome, telomeric region; mitotic spindle pole; and nucleus. [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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.422 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNKS	NM_003747.3	c.2644-4617T>C		intron_variant		ENST00000310430.11	NP_003738.2
TNKS	XM_011543845.4	c.2644-4617T>C		intron_variant			XP_011542147.1
TNKS	XM_011543846.4	c.2644-4617T>C		intron_variant			XP_011542148.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNKS	ENST00000310430.11	c.2644-4617T>C		intron_variant		1	NM_003747.3	ENSP00000311579	P1

Frequencies

GnomAD3 genomes AF: 0.178 AC: 27054 AN: 152068 Hom.: 3137 Cov.: 32

Gnomad AFR AF: 0.0445

Gnomad AMI AF: 0.360

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.438

Gnomad SAS AF: 0.304

Gnomad FIN AF: 0.180

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.212

Gnomad OTH AF: 0.186

GnomAD4 exome AF: 0.250 AC: 1 AN: 4 Hom.: 0 AF XY: 0.250 AC XY: 1 AN XY: 4

Gnomad4 NFE exome AF: 0.250

GnomAD4 genome AF: 0.178 AC: 27076 AN: 152188 Hom.: 3146 Cov.: 32 AF XY: 0.181 AC XY: 13458 AN XY: 74392

Gnomad4 AFR AF: 0.0444

Gnomad4 AMR AF: 0.249

Gnomad4 ASJ AF: 0.176

Gnomad4 EAS AF: 0.437

Gnomad4 SAS AF: 0.304

Gnomad4 FIN AF: 0.180

Gnomad4 NFE AF: 0.212

Gnomad4 OTH AF: 0.188

Alfa AF: 0.210 Hom.: 5186

Bravo AF: 0.180

Asia WGS AF: 0.332 AC: 1154 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.40
DANN	Benign	0.72

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: rs9644708; hg19: chr8-9600917;