chr8-9555947-C-A

Variant summary

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

The NM_003747.3(TNKS):​c.8C>A​(p.Ala3Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000137 in 1,610,376 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 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

TNKS
NM_003747.3 missense

Scores

1
9
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.86
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=0.18741757).
BS2
High AC in GnomAdExome4 at 19 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TNKSNM_003747.3 linkuse as main transcriptc.8C>A p.Ala3Glu missense_variant 1/27 ENST00000310430.11 NP_003738.2
TNKSXM_011543845.4 linkuse as main transcriptc.8C>A p.Ala3Glu missense_variant 1/28 XP_011542147.1
TNKSXM_011543846.4 linkuse as main transcriptc.8C>A p.Ala3Glu 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.8C>A p.Ala3Glu missense_variant 1/271 NM_003747.3 ENSP00000311579 P1O95271-1
TNKSENST00000517770.2 linkuse as main transcriptc.8C>A p.Ala3Glu missense_variant 1/284 ENSP00000428185
TNKSENST00000520408.5 linkuse as main transcriptc.8C>A p.Ala3Glu missense_variant 1/112 ENSP00000428299
TNKSENST00000522110.1 linkuse as main transcriptc.8C>A p.Ala3Glu missense_variant 1/1 ENSP00000430920

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152216
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.000864
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
GnomAD3 exomes
AF:
0.00000821
AC:
2
AN:
243466
Hom.:
0
AF XY:
0.00000755
AC XY:
1
AN XY:
132386
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.000206
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000130
AC:
19
AN:
1458160
Hom.:
0
Cov.:
31
AF XY:
0.00000965
AC XY:
7
AN XY:
725326
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.000542
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.0000499
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152216
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
AN XY:
74370
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.000864
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000283
Hom.:
0
Bravo
AF:
0.0000189

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 GeneticsFeb 23, 2023The c.8C>A (p.A3E) alteration is located in exon 1 (coding exon 1) of the TNKS gene. This alteration results from a C to A substitution at nucleotide position 8, causing the alanine (A) at amino acid position 3 to be replaced by a glutamic acid (E). 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
Uncertain
0.41
BayesDel_addAF
Uncertain
0.063
T
BayesDel_noAF
Benign
-0.15
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.28
.;T;.
Eigen
Uncertain
0.19
Eigen_PC
Uncertain
0.32
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Benign
0.76
T;T;T
M_CAP
Uncertain
0.10
D
MetaRNN
Benign
0.19
T;T;T
MetaSVM
Benign
-0.71
T
MutationAssessor
Benign
0.0
.;N;.
MutationTaster
Benign
0.97
D;D;D
PrimateAI
Uncertain
0.61
T
PROVEAN
Benign
-0.10
N;N;N
REVEL
Benign
0.14
Sift
Pathogenic
0.0
D;D;D
Sift4G
Uncertain
0.032
D;T;D
Polyphen
0.93
P;P;.
Vest4
0.63
MutPred
0.22
Gain of solvent accessibility (P = 0.005);Gain of solvent accessibility (P = 0.005);Gain of solvent accessibility (P = 0.005);
MVP
0.43
MPC
0.44
ClinPred
0.54
D
GERP RS
4.8
Varity_R
0.39
gMVP
0.32

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: rs1302984680; hg19: chr8-9413457; API