chr8-9556145-A-G
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_003747.3(TNKS):āc.206A>Gā(p.Asp69Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000249 in 1,607,324 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 (ā ).
Frequency
Genomes: š 0.0000066 ( 0 hom., cov: 33)
Exomes š: 0.0000021 ( 0 hom. )
Consequence
TNKS
NM_003747.3 missense
NM_003747.3 missense
Scores
1
6
12
Clinical Significance
Conservation
PhyloP100: 2.28
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.14710426).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TNKS | NM_003747.3 | c.206A>G | p.Asp69Gly | missense_variant | 1/27 | ENST00000310430.11 | NP_003738.2 | |
TNKS | XM_011543845.4 | c.206A>G | p.Asp69Gly | missense_variant | 1/28 | XP_011542147.1 | ||
TNKS | XM_011543846.4 | c.206A>G | p.Asp69Gly | missense_variant | 1/27 | XP_011542148.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TNKS | ENST00000310430.11 | c.206A>G | p.Asp69Gly | missense_variant | 1/27 | 1 | NM_003747.3 | ENSP00000311579 | P1 | |
TNKS | ENST00000517770.2 | c.206A>G | p.Asp69Gly | missense_variant | 1/28 | 4 | ENSP00000428185 | |||
TNKS | ENST00000520408.5 | c.206A>G | p.Asp69Gly | missense_variant | 1/11 | 2 | ENSP00000428299 | |||
TNKS | ENST00000522110.1 | c.206A>G | p.Asp69Gly | missense_variant | 1/1 | ENSP00000430920 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152122Hom.: 0 Cov.: 33
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GnomAD4 exome AF: 0.00000206 AC: 3AN: 1455202Hom.: 0 Cov.: 31 AF XY: 0.00000277 AC XY: 2AN XY: 723140
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152122Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74300
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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 submitter | clinical testing | Ambry Genetics | Dec 02, 2021 | The c.206A>G (p.D69G) alteration is located in exon 1 (coding exon 1) of the TNKS gene. This alteration results from a A to G substitution at nucleotide position 206, causing the aspartic acid (D) at amino acid position 69 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
.;T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T;T
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
.;N;.
MutationTaster
Benign
D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;N;N
REVEL
Uncertain
Sift
Uncertain
D;D;D
Sift4G
Benign
T;T;T
Polyphen
B;B;.
Vest4
MutPred
Gain of catalytic residue at D69 (P = 0.0516);Gain of catalytic residue at D69 (P = 0.0516);Gain of catalytic residue at D69 (P = 0.0516);
MVP
MPC
0.49
ClinPred
D
GERP RS
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at