10-91819544-G-T
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_025235.4(TNKS2):c.620G>T(p.Ser207Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000195 in 1,592,146 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000020 ( 0 hom. )
Consequence
TNKS2
NM_025235.4 missense
NM_025235.4 missense
Scores
3
9
7
Clinical Significance
Conservation
PhyloP100: 9.97
Genes affected
TNKS2 (HGNC:15677): (tankyrase 2) Enables NAD+ ADP-ribosyltransferase activity; enzyme binding activity; and protein ADP-ribosylase activity. Involved in several processes, including protein ADP-ribosylation; protein localization to chromosome, telomeric region; and regulation of telomere maintenance. Located in nuclear envelope; pericentriolar material; and perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
BS2
High AC in GnomAdExome4 at 29 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TNKS2 | NM_025235.4 | c.620G>T | p.Ser207Ile | missense_variant | 5/27 | ENST00000371627.5 | NP_079511.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TNKS2 | ENST00000371627.5 | c.620G>T | p.Ser207Ile | missense_variant | 5/27 | 1 | NM_025235.4 | ENSP00000360689 | P1 | |
TNKS2 | ENST00000710380.1 | c.659G>T | p.Ser220Ile | missense_variant | 5/27 | ENSP00000518237 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152094Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.0000201 AC: 29AN: 1440052Hom.: 0 Cov.: 31 AF XY: 0.0000181 AC XY: 13AN XY: 716338
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GnomAD4 genome AF: 0.0000131 AC: 2AN: 152094Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74288
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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 | Sep 20, 2023 | The c.620G>T (p.S207I) alteration is located in exon 5 (coding exon 5) of the TNKS2 gene. This alteration results from a G to T substitution at nucleotide position 620, causing the serine (S) at amino acid position 207 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Benign
T
MetaRNN
Uncertain
D
MetaSVM
Benign
T
MutationAssessor
Benign
N
MutationTaster
Benign
D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D
REVEL
Uncertain
Sift
Benign
D
Sift4G
Benign
T
Polyphen
B
Vest4
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
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