chr8-9556178-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_003747.3(TNKS):​c.239C>T​(p.Ser80Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000141 in 1,612,648 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

TNKS
NM_003747.3 missense

Scores

1
4
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.24
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 made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.088935256).
BS2
High AC in GnomAd4 at 18 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TNKSNM_003747.3 linkuse as main transcriptc.239C>T p.Ser80Phe missense_variant 1/27 ENST00000310430.11 NP_003738.2
TNKSXM_011543845.4 linkuse as main transcriptc.239C>T p.Ser80Phe missense_variant 1/28 XP_011542147.1
TNKSXM_011543846.4 linkuse as main transcriptc.239C>T p.Ser80Phe missense_variant 1/27 XP_011542148.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TNKSENST00000310430.11 linkuse as main transcriptc.239C>T p.Ser80Phe missense_variant 1/271 NM_003747.3 ENSP00000311579 P1O95271-1
TNKSENST00000517770.2 linkuse as main transcriptc.239C>T p.Ser80Phe missense_variant 1/284 ENSP00000428185
TNKSENST00000520408.5 linkuse as main transcriptc.239C>T p.Ser80Phe missense_variant 1/112 ENSP00000428299
TNKSENST00000522110.1 linkuse as main transcriptc.239C>T p.Ser80Phe missense_variant 1/1 ENSP00000430920

Frequencies

GnomAD3 genomes
AF:
0.000118
AC:
18
AN:
152240
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.000865
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000206
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000116
AC:
29
AN:
249502
Hom.:
0
AF XY:
0.000104
AC XY:
14
AN XY:
135040
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.000698
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.000188
Gnomad NFE exome
AF:
0.000151
Gnomad OTH exome
AF:
0.000164
GnomAD4 exome
AF:
0.000144
AC:
210
AN:
1460408
Hom.:
0
Cov.:
31
AF XY:
0.000127
AC XY:
92
AN XY:
726286
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.000881
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.000151
Gnomad4 NFE exome
AF:
0.000157
Gnomad4 OTH exome
AF:
0.0000663
GnomAD4 genome
AF:
0.000118
AC:
18
AN:
152240
Hom.:
0
Cov.:
33
AF XY:
0.000134
AC XY:
10
AN XY:
74388
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.000865
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000206
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000207
Hom.:
0
Bravo
AF:
0.0000982
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000581
AC:
5
ExAC
AF:
0.0000824
AC:
10
EpiCase
AF:
0.000109
EpiControl
AF:
0.000296

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJan 23, 2024The c.239C>T (p.S80F) 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 239, causing the serine (S) at amino acid position 80 to be replaced by a phenylalanine (F). 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
0.10
BayesDel_addAF
Benign
-0.27
T
BayesDel_noAF
Benign
-0.37
CADD
Uncertain
26
DANN
Uncertain
0.99
DEOGEN2
Benign
0.32
.;T;.
Eigen
Benign
-0.00097
Eigen_PC
Benign
0.21
FATHMM_MKL
Uncertain
0.88
D
LIST_S2
Benign
0.82
T;T;T
M_CAP
Uncertain
0.16
D
MetaRNN
Benign
0.089
T;T;T
MetaSVM
Benign
-0.92
T
MutationAssessor
Benign
0.69
.;N;.
MutationTaster
Benign
0.91
D;D;D
PrimateAI
Pathogenic
0.81
D
PROVEAN
Benign
0.010
N;N;N
REVEL
Benign
0.067
Sift
Uncertain
0.014
D;D;D
Sift4G
Benign
0.12
T;T;D
Polyphen
0.0010
B;B;.
Vest4
0.40
MVP
0.24
MPC
0.41
ClinPred
0.13
T
GERP RS
4.8
Varity_R
0.29
gMVP
0.17

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs146118607; hg19: chr8-9413688; API