chr8-9556034-C-T

Variant summary

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

The NM_003747.3(TNKS):​c.95C>T​(p.Pro32Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000558 in 1,611,972 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

TNKS
NM_003747.3 missense

Scores

1
5
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.48

Publications

1 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]

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=0.1535202).
BS2
High AC in GnomAdExome4 at 8 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TNKSNM_003747.3 linkc.95C>T p.Pro32Leu missense_variant Exon 1 of 27 ENST00000310430.11 NP_003738.2 O95271-1
TNKSXM_011543845.4 linkc.95C>T p.Pro32Leu missense_variant Exon 1 of 28 XP_011542147.1
TNKSXM_011543846.4 linkc.95C>T p.Pro32Leu missense_variant Exon 1 of 27 XP_011542148.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TNKSENST00000310430.11 linkc.95C>T p.Pro32Leu missense_variant Exon 1 of 27 1 NM_003747.3 ENSP00000311579.6 O95271-1
TNKSENST00000517770.2 linkc.95C>T p.Pro32Leu missense_variant Exon 1 of 28 4 ENSP00000428185.2 H0YAW5
TNKSENST00000520408.5 linkc.95C>T p.Pro32Leu missense_variant Exon 1 of 11 2 ENSP00000428299.1 E7EWY6
TNKSENST00000522110.1 linkc.95C>T p.Pro32Leu missense_variant Exon 1 of 1 6 ENSP00000430920.1 E5RHD2

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152244
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000548
AC:
8
AN:
1459728
Hom.:
0
Cov.:
31
AF XY:
0.00000826
AC XY:
6
AN XY:
726200
show subpopulations
African (AFR)
AF:
0.0000598
AC:
2
AN:
33470
American (AMR)
AF:
0.00
AC:
0
AN:
44614
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26040
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39684
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86160
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
52188
Middle Eastern (MID)
AF:
0.000175
AC:
1
AN:
5726
European-Non Finnish (NFE)
AF:
0.00000450
AC:
5
AN:
1111546
Other (OTH)
AF:
0.00
AC:
0
AN:
60300
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.519
Heterozygous variant carriers
0
1
2
2
3
4
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152244
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74372
show subpopulations
African (AFR)
AF:
0.0000241
AC:
1
AN:
41466
American (AMR)
AF:
0.00
AC:
0
AN:
15288
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3470
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5192
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4836
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10628
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
68042
Other (OTH)
AF:
0.00
AC:
0
AN:
2094
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.575
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.00000756

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
May 21, 2025
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.95C>T (p.P32L) alteration is located in exon 1 (coding exon 1) of the TNKS gene. This alteration results from a C to T substitution at nucleotide position 95, causing the proline (P) at amino acid position 32 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.088
BayesDel_addAF
Uncertain
0.032
T
BayesDel_noAF
Benign
-0.19
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.39
.;T;.
Eigen
Benign
-0.23
Eigen_PC
Benign
-0.049
FATHMM_MKL
Benign
0.46
N
LIST_S2
Benign
0.86
D;D;D
M_CAP
Uncertain
0.13
D
MetaRNN
Benign
0.15
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.0
.;N;.
PhyloP100
1.5
PrimateAI
Pathogenic
0.81
D
PROVEAN
Benign
-0.22
N;N;N
REVEL
Benign
0.093
Sift
Uncertain
0.0020
D;D;D
Sift4G
Uncertain
0.060
T;D;D
Polyphen
0.0
B;B;.
Vest4
0.44
MutPred
0.34
Loss of glycosylation at P32 (P = 1e-04);Loss of glycosylation at P32 (P = 1e-04);Loss of glycosylation at P32 (P = 1e-04);
MVP
0.24
MPC
0.38
ClinPred
0.79
D
GERP RS
4.0
PromoterAI
0.057
Neutral
Varity_R
0.12
gMVP
0.25
Mutation Taster
=87/13
polymorphism

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

Other links and lift over

dbSNP: rs776203335; hg19: chr8-9413544; API