chr16-29978107-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate

The NM_016151.4(TAOK2):​c.151A>G​(p.Ser51Gly) 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 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: not found (cov: 32)

Consequence

TAOK2
NM_016151.4 missense

Scores

1
1
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.32
Variant links:
Genes affected
TAOK2 (HGNC:16835): (TAO kinase 2) Enables mitogen-activated protein kinase kinase binding activity; neuropilin binding activity; and protein serine/threonine kinase activity. Involved in several processes, including focal adhesion assembly; intracellular signal transduction; and positive regulation of JNK cascade. Located in cytoplasmic vesicle; cytosol; and nuclear lumen. Part of receptor complex. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), TAOK2. . Gene score misZ 3.2101 (greater than the threshold 3.09). Trascript score misZ 3.3599 (greater than threshold 3.09). GenCC has associacion of gene with autism spectrum disorder, immunodeficiency disease.
BP4
Computational evidence support a benign effect (MetaRNN=0.113076806).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TAOK2NM_016151.4 linkuse as main transcriptc.151A>G p.Ser51Gly missense_variant 3/16 ENST00000308893.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TAOK2ENST00000308893.9 linkuse as main transcriptc.151A>G p.Ser51Gly missense_variant 3/161 NM_016151.4 Q9UL54-1
TAOK2ENST00000543033.5 linkuse as main transcriptc.151A>G p.Ser51Gly missense_variant 3/171 Q9UL54-4
TAOK2ENST00000279394.7 linkuse as main transcriptc.151A>G p.Ser51Gly missense_variant 3/191 P1Q9UL54-2

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 provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingInvitaeOct 18, 2022In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. This variant has not been reported in the literature in individuals affected with TAOK2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with glycine, which is neutral and non-polar, at codon 51 of the TAOK2 protein (p.Ser51Gly). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.060
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.44
CADD
Uncertain
24
DANN
Benign
0.97
DEOGEN2
Benign
0.16
T;.;.
Eigen
Benign
-0.35
Eigen_PC
Benign
-0.027
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.84
T;T;T
M_CAP
Benign
0.0051
T
MetaRNN
Benign
0.11
T;T;T
MetaSVM
Benign
-0.96
T
MutationAssessor
Benign
-1.6
N;N;N
MutationTaster
Benign
0.99
D;D;D
PrimateAI
Uncertain
0.59
T
PROVEAN
Benign
-1.6
N;N;N
REVEL
Benign
0.13
Sift
Benign
0.28
T;T;T
Sift4G
Benign
0.21
T;T;T
Polyphen
0.016
B;.;B
Vest4
0.33
MutPred
0.38
Loss of phosphorylation at S51 (P = 0.0891);Loss of phosphorylation at S51 (P = 0.0891);Loss of phosphorylation at S51 (P = 0.0891);
MVP
0.38
MPC
1.0
ClinPred
0.95
D
GERP RS
5.3
Varity_R
0.23
gMVP
0.66

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
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: chr16-29989428; API