8-9753028-C-T

Variant names:

• chr8-9753028-C-T
• rs6989782
• NM_003747.3:c.3153+402C>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.3153+402C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 151,460 control chromosomes in the GnomAD database, including 6,158 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 0.27 (6158 hom., cov: 31)
• Consequence: TNKS NM_003747.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.953
• 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.377 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNKS	NM_003747.3	MANE Select	c.3153+402C>T		intron	N/A	NP_003738.2	O95271-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNKS	ENST00000310430.11	TSL:1 MANE Select	c.3153+402C>T		intron	N/A	ENSP00000311579.6	O95271-1
	TNKS	ENST00000517770.2	TSL:4	c.3153+402C>T		intron	N/A	ENSP00000428185.2	H0YAW5
	TNKS	ENST00000885812.1		c.3081+402C>T		intron	N/A	ENSP00000555871.1

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41409 AN: 151356 Hom.: 6160 Cov.: 31

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.286

Gnomad AMR AF: 0.356

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.391

Gnomad SAS AF: 0.260

Gnomad FIN AF: 0.409

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.288

Gnomad OTH AF: 0.250

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

GnomAD4 genome AF: 0.273 AC: 41422 AN: 151460 Hom.: 6158 Cov.: 31 AF XY: 0.279 AC XY: 20598 AN XY: 73932

African (AFR) AF: 0.182 AC: 7532 AN: 41296

American (AMR) AF: 0.356 AC: 5418 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.173 AC: 599 AN: 3460

East Asian (EAS) AF: 0.391 AC: 2016 AN: 5150

South Asian (SAS) AF: 0.259 AC: 1242 AN: 4792

European-Finnish (FIN) AF: 0.409 AC: 4243 AN: 10370

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.288 AC: 19530 AN: 67856

Other (OTH) AF: 0.250 AC: 527 AN: 2106

Alfa AF: 0.281 Hom.: 3356

Bravo AF: 0.271

Asia WGS AF: 0.308 AC: 1073 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.37
DANN	Benign	0.71
PhyloP100		-0.95
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: rs6989782; hg19: chr8-9610538; COSMIC: COSV60063686; COSMIC: COSV60063686;