Variant chr8-9556383-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_003747.3(TNKS):c.444G>A(p.Ser148=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00443 in 1,614,172 control chromosomes in the GnomAD database, including 212 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.021 ( 109 hom., cov: 32)

Exomes 𝑓: 0.0027 ( 103 hom. )

Consequence

TNKS
NM_003747.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.271

Variant links:

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]

TNKS links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant 8-9556383-G-A is Benign according to our data. Variant chr8-9556383-G-A is described in ClinVar as [Benign]. Clinvar id is 787328.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.271 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.068 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TNKS	NM_003747.3 linkuse as main transcript	c.444G>A	p.Ser148=	synonymous_variant	1/27	ENST00000310430.11	NP_003738.2
TNKS	XM_011543845.4 linkuse as main transcript	c.444G>A	p.Ser148=	synonymous_variant	1/28		XP_011542147.1
TNKS	XM_011543846.4 linkuse as main transcript	c.444G>A	p.Ser148=	synonymous_variant	1/27		XP_011542148.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNKS	ENST00000310430.11 linkuse as main transcript	c.444G>A	p.Ser148=	synonymous_variant	1/27	1	NM_003747.3	ENSP00000311579	P1	O95271-1
TNKS	ENST00000517770.2 linkuse as main transcript	c.444G>A	p.Ser148=	synonymous_variant	1/28	4		ENSP00000428185
TNKS	ENST00000520408.5 linkuse as main transcript	c.444G>A	p.Ser148=	synonymous_variant	1/11	2		ENSP00000428299
TNKS	ENST00000522110.1 linkuse as main transcript	c.444G>A	p.Ser148=	synonymous_variant	1/1			ENSP00000430920

Frequencies

GnomAD3 genomes

AF:

0.0208

AC:

3161

AN:

152166

Hom.:

110

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0702

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00818

Gnomad ASJ

AF:

0.0130

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000544

Gnomad OTH

AF:

0.0186

GnomAD3 exomes

AF:

0.00587

AC:

1476

AN:

251444

Hom.:

AF XY:

0.00470

AC XY:

639

AN XY:

135916

show subpopulations

Gnomad AFR exome

AF:

0.0676

Gnomad AMR exome

AF:

0.00396

Gnomad ASJ exome

AF:

0.0147

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000633

Gnomad OTH exome

AF:

0.00293

GnomAD4 exome

AF:

0.00272

AC:

3983

AN:

1461888

Hom.:

103

Cov.:

AF XY:

0.00245

AC XY:

1781

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.0742

Gnomad4 AMR exome

AF:

0.00447

Gnomad4 ASJ exome

AF:

0.0134

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000538

Gnomad4 OTH exome

AF:

0.00530

GnomAD4 genome

AF:

0.0208

AC:

3166

AN:

152284

Hom.:

109

Cov.:

AF XY:

0.0214

AC XY:

1593

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.0702

Gnomad4 AMR

AF:

0.00817

Gnomad4 ASJ

AF:

0.0130

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000544

Gnomad4 OTH

AF:

0.0184

Alfa

AF:

0.00925

Hom.:

Bravo

AF:

0.0232

Asia WGS

AF:

0.00404

AC:

AN:

3478

EpiCase

AF:

0.00104

EpiControl

AF:

0.00101

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 16, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

9.7

DANN

Benign

0.93

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over