Genetic Variant TNKS:c.2644-4617T>C (chr8-9743407-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003747.3(TNKS):c.2644-4617T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 152,192 control chromosomes in the GnomAD database, including 3,146 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 0.18 ( 3146 hom., cov: 32)

Exomes 𝑓: 0.25 ( 0 hom. )

Consequence

TNKS
NM_003747.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.914

Publications

8 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.422 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.2644-4617T>C		intron	N/A	NP_003738.2	O95271-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TNKS	ENST00000310430.11	TSL:1 MANE Select	c.2644-4617T>C	intron	N/A	ENSP00000311579.6	O95271-1
TNKS	ENST00000517770.2	TSL:4	c.2644-4617T>C	intron	N/A	ENSP00000428185.2	H0YAW5
TNKS	ENST00000885812.1		c.2644-4617T>C	intron	N/A	ENSP00000555871.1

Frequencies

GnomAD3 genomes

AF:

0.178

AC:

27054

AN:

152068

Hom.:

3137

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0445

Gnomad AMI

AF:

0.360

Gnomad AMR

AF:

0.248

Gnomad ASJ

AF:

0.176

Gnomad EAS

AF:

0.438

Gnomad SAS

AF:

0.304

Gnomad FIN

AF:

0.180

Gnomad MID

AF:

0.184

Gnomad NFE

AF:

0.212

Gnomad OTH

AF:

0.186

GnomAD4 exome

AF:

0.250

AC:

AN:

Hom.:

AF XY:

0.250

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.250

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.178

AC:

27076

AN:

152188

Hom.:

3146

Cov.:

AF XY:

0.181

AC XY:

13458

AN XY:

74392

show subpopulations

African (AFR)

AF:

0.0444

AC:

1846

AN:

41558

American (AMR)

AF:

0.249

AC:

3804

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.176

AC:

610

AN:

3470

East Asian (EAS)

AF:

0.437

AC:

2254

AN:

5154

South Asian (SAS)

AF:

0.304

AC:

1466

AN:

4828

European-Finnish (FIN)

AF:

0.180

AC:

1902

AN:

10594

Middle Eastern (MID)

AF:

0.184

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.212

AC:

14415

AN:

67978

Other (OTH)

AF:

0.188

AC:

397

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1067

2135

3202

4270

5337

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

304

608

912

1216

1520

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.206

Hom.:

6935

Bravo

AF:

0.180

Asia WGS

AF:

0.332

AC:

1154

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.40

(source)

DANN

Benign

0.72

PhyloP100

-0.91

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over