2-171014906-C-T
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Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP2BP4_Strong
The NM_012290.5(TLK1):c.1279G>A(p.Val427Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00047 in 1,613,980 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00072 ( 1 hom., cov: 31)
Exomes 𝑓: 0.00044 ( 1 hom. )
Consequence
TLK1
NM_012290.5 missense
NM_012290.5 missense
Scores
5
14
Clinical Significance
Conservation
PhyloP100: 6.17
Genes affected
TLK1 (HGNC:11841): (tousled like kinase 1) The protein encoded by this gene is a serine/threonine kinase that may be involved in the regulation of chromatin assembly. The encoded protein is only active when it is phosphorylated, and this phosphorylation is cell cycle-dependent, with the maximal activity of this protein coming during S phase. The catalytic activity of this protein is diminished by DNA damage and by blockage of DNA replication. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2011]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PP2
Missense variant where missense usually causes diseases, TLK1
BP4
Computational evidence support a benign effect (MetaRNN=0.010010481).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TLK1 | NM_012290.5 | c.1279G>A | p.Val427Ile | missense_variant | 13/21 | ENST00000431350.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TLK1 | ENST00000431350.7 | c.1279G>A | p.Val427Ile | missense_variant | 13/21 | 1 | NM_012290.5 |
Frequencies
GnomAD3 genomes AF: 0.000729 AC: 111AN: 152180Hom.: 1 Cov.: 31
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GnomAD3 exomes AF: 0.000696 AC: 175AN: 251280Hom.: 0 AF XY: 0.000700 AC XY: 95AN XY: 135802
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GnomAD4 exome AF: 0.000443 AC: 648AN: 1461682Hom.: 1 Cov.: 30 AF XY: 0.000443 AC XY: 322AN XY: 727148
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GnomAD4 genome AF: 0.000722 AC: 110AN: 152298Hom.: 1 Cov.: 31 AF XY: 0.000739 AC XY: 55AN XY: 74472
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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 | Jul 09, 2021 | The c.1279G>A (p.V427I) alteration is located in exon 13 (coding exon 13) of the TLK1 gene. This alteration results from a G to A substitution at nucleotide position 1279, causing the valine (V) at amino acid position 427 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
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.;.;.
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;.;.;.
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N
REVEL
Benign
Sift
Benign
T;T;T;T
Sift4G
Benign
T;T;T;T
Polyphen
B;B;.;.
Vest4
MVP
MPC
ClinPred
T
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