11-57302155-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_033396.3(TNKS1BP1):​c.4753G>C​(p.Ala1585Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

TNKS1BP1
NM_033396.3 missense

Scores

2
10
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.64
Variant links:
Genes affected
TNKS1BP1 (HGNC:19081): (tankyrase 1 binding protein 1) Enables ankyrin repeat binding activity and enzyme binding activity. Involved in cellular response to ionizing radiation; double-strand break repair; and positive regulation of protein phosphorylation. Located in several cellular components, including actin cytoskeleton; adherens junction; and heterochromatin. Part of CCR4-NOT complex. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.782

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TNKS1BP1NM_033396.3 linkc.4753G>C p.Ala1585Pro missense_variant Exon 8 of 12 ENST00000358252.8 NP_203754.2 Q9C0C2-1A0A024R542
TNKS1BP1XM_006718725.4 linkc.4753G>C p.Ala1585Pro missense_variant Exon 8 of 12 XP_006718788.1 Q9C0C2-1A0A024R542
TNKS1BP1XM_047427785.1 linkc.2725G>C p.Ala909Pro missense_variant Exon 4 of 8 XP_047283741.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TNKS1BP1ENST00000358252.8 linkc.4753G>C p.Ala1585Pro missense_variant Exon 8 of 12 1 NM_033396.3 ENSP00000350990.3 Q9C0C2-1
TNKS1BP1ENST00000532437.1 linkc.4753G>C p.Ala1585Pro missense_variant Exon 7 of 11 1 ENSP00000437271.1 Q9C0C2-1
TNKS1BP1ENST00000528882.5 linkn.*3103-2194G>C intron_variant Intron 6 of 6 5 ENSP00000431616.1 E9PKK0
TNKS1BP1ENST00000427750.2 linkn.1091G>C non_coding_transcript_exon_variant Exon 2 of 6 2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
May 21, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.4753G>C (p.A1585P) alteration is located in exon 8 (coding exon 7) of the TNKS1BP1 gene. This alteration results from a G to C substitution at nucleotide position 4753, causing the alanine (A) at amino acid position 1585 to be replaced by a proline (P). 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
0.53
BayesDel_addAF
Uncertain
0.079
D
BayesDel_noAF
Benign
-0.13
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.055
T;T
Eigen
Uncertain
0.67
Eigen_PC
Uncertain
0.65
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.84
.;T
M_CAP
Benign
0.059
D
MetaRNN
Pathogenic
0.78
D;D
MetaSVM
Benign
-0.53
T
MutationAssessor
Uncertain
2.5
M;M
PrimateAI
Uncertain
0.66
T
PROVEAN
Uncertain
-4.4
D;D
REVEL
Benign
0.21
Sift
Uncertain
0.0030
D;D
Sift4G
Uncertain
0.018
D;D
Polyphen
1.0
D;D
Vest4
0.81
MutPred
0.40
Loss of MoRF binding (P = 0.0577);Loss of MoRF binding (P = 0.0577);
MVP
0.77
MPC
0.49
ClinPred
0.99
D
GERP RS
5.3
Varity_R
0.82
gMVP
0.28

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-57069629; API