8-9609596-C-T

Variant names:

• chr8-9609596-C-T
• rs10903314
• NM_003747.3:c.899-5986C>T

Variant summary

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

The NM_003747.3(TNKS):​c.899-5986C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 151,980 control chromosomes in the GnomAD database, including 6,589 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 0.29 (6589 hom., cov: 32)
• Consequence: TNKS NM_003747.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.329
• Publications: 7 publications found

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

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 = 0.371 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003747.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNKS	NM_003747.3	MANE Select	c.899-5986C>T		intron	N/A	NP_003738.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNKS	ENST00000310430.11	TSL:1 MANE Select	c.899-5986C>T		intron	N/A	ENSP00000311579.6
	TNKS	ENST00000517770.2	TSL:4	c.899-5986C>T		intron	N/A	ENSP00000428185.2
	TNKS	ENST00000518281.5	TSL:2	c.188-5986C>T		intron	N/A	ENSP00000429890.1

Frequencies

GnomAD3 genomes AF: 0.288 AC: 43677 AN: 151862 Hom.: 6567 Cov.: 32

Gnomad AFR AF: 0.357

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.385

Gnomad SAS AF: 0.299

Gnomad FIN AF: 0.386

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.247

Gnomad OTH AF: 0.244

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

GnomAD4 genome AF: 0.288 AC: 43741 AN: 151980 Hom.: 6589 Cov.: 32 AF XY: 0.292 AC XY: 21708 AN XY: 74286

African (AFR) AF: 0.358 AC: 14816 AN: 41422

American (AMR) AF: 0.219 AC: 3349 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.157 AC: 545 AN: 3468

East Asian (EAS) AF: 0.385 AC: 1987 AN: 5160

South Asian (SAS) AF: 0.298 AC: 1438 AN: 4820

European-Finnish (FIN) AF: 0.386 AC: 4068 AN: 10552

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.247 AC: 16783 AN: 67970

Other (OTH) AF: 0.247 AC: 521 AN: 2108

Alfa AF: 0.257 Hom.: 2789

Bravo AF: 0.280

Asia WGS AF: 0.361 AC: 1253 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	5.0
DANN	Benign	0.75
PhyloP100		0.33
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: rs10903314; hg19: chr8-9467106;