rs3758499

Positions:

• chr10-91848385-G-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_025235.4(TNKS2):​c.2361G>A​(p.Ala787=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.332 in 1,613,252 control chromosomes in the GnomAD database, including 93,314 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 0.33 (8618 hom., cov: 32)
  • Exomes 𝑓: 0.33 (84696 hom.)
• Consequence: TNKS2 NM_025235.4 splice_region, synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0690

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.512 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNKS2	NM_025235.4	c.2361G>A	p.Ala787=	splice_region_variant, synonymous_variant	19/27	ENST00000371627.5
TNKS2	XM_011540213.2	c.2424G>A	p.Ala808=	splice_region_variant, synonymous_variant	19/27
TNKS2	XM_017016699.2	c.2040G>A	p.Ala680=	splice_region_variant, synonymous_variant	18/26
TNKS2	XM_017016700.3	c.1065G>A	p.Ala355=	splice_region_variant, synonymous_variant	7/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNKS2	ENST00000371627.5	c.2361G>A	p.Ala787=	splice_region_variant, synonymous_variant	19/27	1	NM_025235.4	P1
TNKS2	ENST00000710380.1	c.2400G>A	p.Ala800=	splice_region_variant, synonymous_variant	19/27

Frequencies

GnomAD3 genomes AF: 0.326 AC: 49576 AN: 151858 Hom.: 8613 Cov.: 32

Gnomad AFR AF: 0.251

Gnomad AMI AF: 0.343

Gnomad AMR AF: 0.381

Gnomad ASJ AF: 0.387

Gnomad EAS AF: 0.499

Gnomad SAS AF: 0.531

Gnomad FIN AF: 0.465

Gnomad MID AF: 0.248

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.284

GnomAD3 exomes AF: 0.381 AC: 95354 AN: 250466 Hom.: 19390 AF XY: 0.382 AC XY: 51666 AN XY: 135352

Gnomad AFR exome AF: 0.250

Gnomad AMR exome AF: 0.485

Gnomad ASJ exome AF: 0.402

Gnomad EAS exome AF: 0.471

Gnomad SAS exome AF: 0.499

Gnomad FIN exome AF: 0.449

Gnomad NFE exome AF: 0.308

Gnomad OTH exome AF: 0.345

GnomAD4 exome AF: 0.333 AC: 486025 AN: 1461276 Hom.: 84696 Cov.: 36 AF XY: 0.337 AC XY: 244630 AN XY: 726878

Gnomad4 AFR exome AF: 0.241

Gnomad4 AMR exome AF: 0.466

Gnomad4 ASJ exome AF: 0.400

Gnomad4 EAS exome AF: 0.490

Gnomad4 SAS exome AF: 0.492

Gnomad4 FIN exome AF: 0.440

Gnomad4 NFE exome AF: 0.305

Gnomad4 OTH exome AF: 0.336

GnomAD4 genome AF: 0.326 AC: 49595 AN: 151976 Hom.: 8618 Cov.: 32 AF XY: 0.339 AC XY: 25179 AN XY: 74274

Gnomad4 AFR AF: 0.251

Gnomad4 AMR AF: 0.382

Gnomad4 ASJ AF: 0.387

Gnomad4 EAS AF: 0.499

Gnomad4 SAS AF: 0.529

Gnomad4 FIN AF: 0.465

Gnomad4 NFE AF: 0.309

Gnomad4 OTH AF: 0.283

Alfa AF: 0.301 Hom.: 8896

Bravo AF: 0.310

Asia WGS AF: 0.493 AC: 1713 AN: 3478

EpiCase AF: 0.295

EpiControl AF: 0.294

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.4
DANN	Benign	0.39

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.29		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.29		Position offset: -2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3758499; hg19: chr10-93608142; COSMIC: COSV65415049;