rs1174664920

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003747.3(TNKS):​c.110C>G​(p.Pro37Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,104 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. P37L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

TNKS
NM_003747.3 missense

Scores

2
4
13

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.29

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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.12783012).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TNKSNM_003747.3 linkc.110C>G p.Pro37Arg missense_variant Exon 1 of 27 ENST00000310430.11 NP_003738.2 O95271-1
TNKSXM_011543845.4 linkc.110C>G p.Pro37Arg missense_variant Exon 1 of 28 XP_011542147.1
TNKSXM_011543846.4 linkc.110C>G p.Pro37Arg 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.110C>G p.Pro37Arg missense_variant Exon 1 of 27 1 NM_003747.3 ENSP00000311579.6 O95271-1
TNKSENST00000517770.2 linkc.110C>G p.Pro37Arg missense_variant Exon 1 of 28 4 ENSP00000428185.2 H0YAW5
TNKSENST00000520408.5 linkc.110C>G p.Pro37Arg missense_variant Exon 1 of 11 2 ENSP00000428299.1 E7EWY6
TNKSENST00000522110.1 linkc.110C>G p.Pro37Arg missense_variant Exon 1 of 1 6 ENSP00000430920.1 E5RHD2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.86e-7
AC:
1
AN:
1458104
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
725280
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33440
American (AMR)
AF:
0.00
AC:
0
AN:
44510
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25950
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39662
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86066
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
51604
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5710
European-Non Finnish (NFE)
AF:
9.00e-7
AC:
1
AN:
1110968
Other (OTH)
AF:
0.00
AC:
0
AN:
60194
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
0
1
1
2
2
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
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Uncertain
0.070
D
BayesDel_noAF
Benign
-0.14
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.33
.;T;.
Eigen
Benign
-0.16
Eigen_PC
Benign
-0.032
FATHMM_MKL
Benign
0.52
D
LIST_S2
Benign
0.78
T;T;T
M_CAP
Uncertain
0.25
D
MetaRNN
Benign
0.13
T;T;T
MetaSVM
Benign
-0.76
T
MutationAssessor
Benign
0.0
.;N;.
PhyloP100
1.3
PrimateAI
Pathogenic
0.87
D
PROVEAN
Benign
-0.080
N;N;N
REVEL
Benign
0.084
Sift
Pathogenic
0.0
D;D;D
Sift4G
Uncertain
0.019
D;D;D
Polyphen
0.53
P;B;.
Vest4
0.31
MutPred
0.35
Loss of glycosylation at P37 (P = 0.0106);Loss of glycosylation at P37 (P = 0.0106);Loss of glycosylation at P37 (P = 0.0106);
MVP
0.26
MPC
0.39
ClinPred
0.39
T
GERP RS
4.0
PromoterAI
0.014
Neutral
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.35
gMVP
0.13
Mutation Taster
=93/7
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: rs1174664920; hg19: chr8-9413559; API