chr8-9556224-A-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_003747.3(TNKS):​c.285A>T​(p.Thr95=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000131 in 1,614,158 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 Benign (★).

Frequency

Genomes: 𝑓 0.00079 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000062 ( 0 hom. )

Consequence

TNKS
NM_003747.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.61
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 Benign. Variant got -11 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.68).
BP6
Variant 8-9556224-A-T is Benign according to our data. Variant chr8-9556224-A-T is described in ClinVar as [Benign]. Clinvar id is 789760.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-1.61 with no splicing effect.
BS2
High AC in GnomAd4 at 121 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TNKSNM_003747.3 linkuse as main transcriptc.285A>T p.Thr95= synonymous_variant 1/27 ENST00000310430.11 NP_003738.2
TNKSXM_011543845.4 linkuse as main transcriptc.285A>T p.Thr95= synonymous_variant 1/28 XP_011542147.1
TNKSXM_011543846.4 linkuse as main transcriptc.285A>T p.Thr95= synonymous_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.285A>T p.Thr95= synonymous_variant 1/271 NM_003747.3 ENSP00000311579 P1O95271-1
TNKSENST00000517770.2 linkuse as main transcriptc.285A>T p.Thr95= synonymous_variant 1/284 ENSP00000428185
TNKSENST00000520408.5 linkuse as main transcriptc.285A>T p.Thr95= synonymous_variant 1/112 ENSP00000428299
TNKSENST00000522110.1 linkuse as main transcriptc.285A>T p.Thr95= synonymous_variant 1/1 ENSP00000430920

Frequencies

GnomAD3 genomes
AF:
0.000802
AC:
122
AN:
152190
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00280
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000196
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:
0.00144
GnomAD3 exomes
AF:
0.000199
AC:
50
AN:
251376
Hom.:
0
AF XY:
0.000110
AC XY:
15
AN XY:
135890
show subpopulations
Gnomad AFR exome
AF:
0.00277
Gnomad AMR exome
AF:
0.000145
Gnomad ASJ exome
AF:
0.00
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:
0.0000622
AC:
91
AN:
1461850
Hom.:
0
Cov.:
31
AF XY:
0.0000509
AC XY:
37
AN XY:
727230
show subpopulations
Gnomad4 AFR exome
AF:
0.00230
Gnomad4 AMR exome
AF:
0.000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.000794
AC:
121
AN:
152308
Hom.:
0
Cov.:
33
AF XY:
0.000725
AC XY:
54
AN XY:
74472
show subpopulations
Gnomad4 AFR
AF:
0.00277
Gnomad4 AMR
AF:
0.000196
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00142
Alfa
AF:
0.000254
Hom.:
0
Bravo
AF:
0.000899
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

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

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJun 26, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.68
CADD
Benign
4.3
DANN
Benign
0.85
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

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: rs139926450; hg19: chr8-9413734; API