Genetic Variant TNKS:p.Leu35Phe (chr8-9556042-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_003747.3(TNKS):c.103C>T(p.Leu35Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000164 in 1,459,172 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L35V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

TNKS
NM_003747.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.893

Publications

0 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.113157004).

BS2

High AC in GnomAdExome4 at 24 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNKS	NM_003747.3 link	c.103C>T	p.Leu35Phe	missense_variant	Exon 1 of 27	ENST00000310430.11	NP_003738.2	O95271-1
TNKS	XM_011543845.4 link	c.103C>T	p.Leu35Phe	missense_variant	Exon 1 of 28		XP_011542147.1
TNKS	XM_011543846.4 link	c.103C>T	p.Leu35Phe	missense_variant	Exon 1 of 27		XP_011542148.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TNKS	ENST00000310430.11 link	c.103C>T	p.Leu35Phe	missense_variant	Exon 1 of 27	1	NM_003747.3	ENSP00000311579.6	O95271-1
TNKS	ENST00000517770.2 link	c.103C>T	p.Leu35Phe	missense_variant	Exon 1 of 28	4		ENSP00000428185.2	H0YAW5
TNKS	ENST00000520408.5 link	c.103C>T	p.Leu35Phe	missense_variant	Exon 1 of 11	2		ENSP00000428299.1	E7EWY6
TNKS	ENST00000522110.1 link	c.103C>T	p.Leu35Phe	missense_variant	Exon 1 of 1	6		ENSP00000430920.1	E5RHD2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000164

AC:

AN:

1459172

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

725918

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33468

American (AMR)

AF:

0.00

AC:

AN:

44580

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26012

East Asian (EAS)

AF:

0.00

AC:

AN:

39684

South Asian (SAS)

AF:

0.00

AC:

AN:

86114

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51970

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5720

European-Non Finnish (NFE)

AF:

0.0000216

AC:

AN:

1111368

Other (OTH)

AF:

0.00

AC:

AN:

60256

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Uncertain

0.030

BayesDel_noAF

Benign

-0.19

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.28

.;T;.

Eigen

Benign

-0.16

Eigen_PC

Benign

-0.053

FATHMM_MKL

Benign

0.48

LIST_S2

Benign

0.78

T;T;T

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.11

T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.0

.;N;.

PhyloP100

0.89

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-0.10

N;N;N

REVEL

Benign

0.039

Sift

Pathogenic

0.0

D;D;D

Sift4G

Benign

0.24

T;T;T

Polyphen

0.84

P;B;.

Vest4

0.38

MutPred

0.19

Loss of glycosylation at P37 (P = 0.2905);Loss of glycosylation at P37 (P = 0.2905);Loss of glycosylation at P37 (P = 0.2905);

MVP

0.31

MPC

0.41

ClinPred

0.42

GERP RS

2.9

PromoterAI

-0.030

Neutral

(source)

Varity_R

0.25

gMVP

0.056

Mutation Taster

=96/4

polymorphism

(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.

8-9556042-C-T

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