Variant rs3758499 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_025235.4(TNKS2):c.2361G>A(p.Ala787Ala) 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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0690

Variant links:

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]

TNKS2 links:

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ACMG classification

Classification made for transcript

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	Protein	UniProt
TNKS2	NM_025235.4 linkuse as main transcript	c.2361G>A	p.Ala787Ala	splice_region_variant, synonymous_variant	19/27	ENST00000371627.5	NP_079511.1	Q9H2K2
TNKS2	XM_011540213.2 linkuse as main transcript	c.2424G>A	p.Ala808Ala	splice_region_variant, synonymous_variant	19/27		XP_011538515.1
TNKS2	XM_017016699.2 linkuse as main transcript	c.2040G>A	p.Ala680Ala	splice_region_variant, synonymous_variant	18/26		XP_016872188.1
TNKS2	XM_017016700.3 linkuse as main transcript	c.1065G>A	p.Ala355Ala	splice_region_variant, synonymous_variant	7/15		XP_016872189.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNKS2	ENST00000371627.5 linkuse as main transcript	c.2361G>A	p.Ala787Ala	splice_region_variant, synonymous_variant	19/27	1	NM_025235.4	ENSP00000360689.4		Q9H2K2
TNKS2	ENST00000710380.1 linkuse as main transcript	c.2400G>A	p.Ala800Ala	splice_region_variant, synonymous_variant	19/27			ENSP00000518237.1

Frequencies

GnomAD3 genomes

AF:

0.326

AC:

49576

AN:

151858

Hom.:

8613

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.337

AC XY:

244630

AN XY:

726878

show subpopulations

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.:

AF XY:

0.339

AC XY:

25179

AN XY:

74274

show subpopulations

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over