10-91864260-C-G

Position:

• chr10-91864260-C-G

Variant summary

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

The NM_025235.4(TNKS2):​c.*1261C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.517 in 152,368 control chromosomes in the GnomAD database, including 20,854 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 0.52 (20767 hom., cov: 31)
  • Exomes 𝑓: 0.62 (87 hom.)
• Consequence: TNKS2 NM_025235.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.470

Genes affected

TNKS2 (HGNC:15677): (tankyrase 2) Enables NAD+ ADP-ribosyltransferase activity; enzyme binding activity; and protein ADP-ribosylase activity. Involved in several processes, including protein ADP-ribosylation; protein localization to chromosome, telomeric region; and regulation of telomere maintenance. Located in nuclear envelope; pericentriolar material; and perinuclear region of cytoplasm. [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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.698 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNKS2	NM_025235.4	c.*1261C>G		3_prime_UTR_variant	27/27	ENST00000371627.5	NP_079511.1
TNKS2	XM_011540213.2	c.*1261C>G		3_prime_UTR_variant	27/27		XP_011538515.1
TNKS2	XM_017016699.2	c.*1261C>G		3_prime_UTR_variant	26/26		XP_016872188.1
TNKS2	XM_017016700.3	c.*1261C>G		3_prime_UTR_variant	15/15		XP_016872189.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNKS2	ENST00000371627.5	c.*1261C>G		3_prime_UTR_variant	27/27	1	NM_025235.4	ENSP00000360689.4
TNKS2	ENST00000710380.1	c.*1261C>G		3_prime_UTR_variant	27/27			ENSP00000518237.1

Frequencies

GnomAD3 genomes AF: 0.517 AC: 78518 AN: 151816 Hom.: 20745 Cov.: 31

Gnomad AFR AF: 0.469

Gnomad AMI AF: 0.561

Gnomad AMR AF: 0.538

Gnomad ASJ AF: 0.617

Gnomad EAS AF: 0.717

Gnomad SAS AF: 0.706

Gnomad FIN AF: 0.626

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.491

Gnomad OTH AF: 0.488

GnomAD4 exome AF: 0.620 AC: 269 AN: 434 Hom.: 87 Cov.: 0 AF XY: 0.630 AC XY: 165 AN XY: 262

Gnomad4 FIN exome AF: 0.620

Gnomad4 NFE exome AF: 0.750

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.517 AC: 78581 AN: 151934 Hom.: 20767 Cov.: 31 AF XY: 0.528 AC XY: 39206 AN XY: 74256

Gnomad4 AFR AF: 0.469

Gnomad4 AMR AF: 0.538

Gnomad4 ASJ AF: 0.617

Gnomad4 EAS AF: 0.717

Gnomad4 SAS AF: 0.704

Gnomad4 FIN AF: 0.626

Gnomad4 NFE AF: 0.491

Gnomad4 OTH AF: 0.485

Alfa AF: 0.502 Hom.: 2482

Bravo AF: 0.502

Asia WGS AF: 0.699 AC: 2433 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.86
DANN	Benign	0.50

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: rs1539042; hg19: chr10-93624017; COSMIC: COSV105303031;