Genetic Variant NM_003747.3: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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
TNKS	NM_003747.3 link	c.2644-4617T>C	intron_variant	Intron 17 of 26	ENST00000310430.11	NP_003738.2	O95271-1
TNKS	XM_011543845.4 link	c.2644-4617T>C	intron_variant	Intron 17 of 27		XP_011542147.1
TNKS	XM_011543846.4 link	c.2644-4617T>C	intron_variant	Intron 17 of 26		XP_011542148.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNKS	ENST00000310430.11 link	c.2644-4617T>C		intron_variant	Intron 17 of 26	1	NM_003747.3	ENSP00000311579.6		O95271-1

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 v4.3

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over