17-29477686-C-T
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PM1PM2PP2PP3_StrongPP5_Moderate
The NM_020791.4(TAOK1):c.332C>T(p.Ser111Phe) variant causes a missense change involving the alteration of a conserved nucleotide. 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 Likely pathogenic (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
TAOK1
NM_020791.4 missense
NM_020791.4 missense
Scores
13
4
2
Clinical Significance
Conservation
PhyloP100: 7.84
Genes affected
TAOK1 (HGNC:29259): (TAO kinase 1) Enables alpha-tubulin binding activity; beta-tubulin binding activity; and kinase activity. Involved in several processes, including mitotic G2 DNA damage checkpoint signaling; negative regulation of microtubule depolymerization; and positive regulation of JNK cascade. Located in microtubule cytoskeleton 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 Pathogenic. Variant got 11 ACMG points.
PM1
?
In a domain Protein kinase (size 253) in uniprot entity TAOK1_HUMAN there are 12 pathogenic changes around while only 0 benign (100%) in NM_020791.4
PM2
?
Very rare variant in population databases, with high coverage;
PP2
?
Missense variant where missense usually causes diseases, TAOK1
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.95
PP5
?
Variant 17-29477686-C-T is Pathogenic according to our data. Variant chr17-29477686-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 982831.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-29477686-C-T is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TAOK1 | NM_020791.4 | c.332C>T | p.Ser111Phe | missense_variant | 5/20 | ENST00000261716.8 | |
TAOK1 | NM_025142.1 | c.332C>T | p.Ser111Phe | missense_variant | 5/18 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TAOK1 | ENST00000261716.8 | c.332C>T | p.Ser111Phe | missense_variant | 5/20 | 1 | NM_020791.4 | P1 | |
TAOK1 | ENST00000536202.1 | c.332C>T | p.Ser111Phe | missense_variant | 5/18 | 1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1259352Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0AN XY: 619810
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1259352
Hom.:
Cov.:
25
AF XY:
AC XY:
0
AN XY:
619810
Gnomad4 AFR exome
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Gnomad4 AMR exome
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Gnomad4 EAS exome
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Gnomad4 SAS exome
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Gnomad4 FIN exome
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Neurodevelopmental disorder Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Institute of Human Genetics, University of Leipzig Medical Center | Jan 01, 2019 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Benign
T;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;M
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D
REVEL
Uncertain
Sift
Pathogenic
D;D
Sift4G
Pathogenic
D;D
Polyphen
D;.
Vest4
MutPred
Loss of disorder (P = 0.0434);Loss of disorder (P = 0.0434);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at