dbSNP rs760730356: TAOK3:p.His129Gln (chr12-118238123-A-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_016281.4(TAOK3):c.387T>A(p.His129Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,728 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

TAOK3
NM_016281.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.716

Publications

0 publications found

Variant links:

Genes affected

TAOK3 (HGNC:18133): (TAO kinase 3) The protein encoded by this gene is a serine/threonine protein kinase that activates the p38/MAPK14 stress-activated MAPK cascade but inhibits the basal activity of the MAPK8/JNK cascade. The encoded protein is a member of the GCK subfamily of STE20-like kinases. [provided by RefSeq, Oct 2016]

TAOK3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09769875).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAOK3	NM_016281.4 link	c.387T>A	p.His129Gln	missense_variant	Exon 7 of 21	ENST00000392533.8	NP_057365.3	Q9H2K8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAOK3	ENST00000392533.8 link	c.387T>A	p.His129Gln	missense_variant	Exon 7 of 21	1	NM_016281.4	ENSP00000376317.3		Q9H2K8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000797

AC:

AN:

251012

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460728

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726712

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33456

American (AMR)

AF:

0.00

AC:

AN:

44700

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26090

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39672

South Asian (SAS)

AF:

0.00

AC:

AN:

86164

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53334

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111212

Other (OTH)

AF:

0.00

AC:

AN:

60336

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 28, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.387T>A (p.H129Q) alteration is located in exon 7 (coding exon 5) of the TAOK3 gene. This alteration results from a T to A substitution at nucleotide position 387, causing the histidine (H) at amino acid position 129 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Benign

0.87

DEOGEN2

Benign

0.19

T;T;T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.80

.;T;T;D

M_CAP

Benign

0.013

MetaRNN

Benign

0.098

T;T;T;T

MetaSVM

Benign

-0.77

MutationAssessor

Benign

-0.045

N;N;.;.

PhyloP100

-0.72

PrimateAI

Uncertain

0.75

PROVEAN

Uncertain

-4.2

D;D;D;D

REVEL

Benign

0.12

Sift

Benign

0.17

T;T;T;T

Sift4G

Benign

0.68

T;T;T;T

Polyphen

0.59

P;P;.;.

Vest4

0.35

MutPred

0.49

Gain of catalytic residue at H129 (P = 0);Gain of catalytic residue at H129 (P = 0);.;Gain of catalytic residue at H129 (P = 0);

MVP

0.34

MPC

0.43

ClinPred

0.21

GERP RS

-10

Varity_R

0.55

gMVP

0.67

Mutation Taster

=50/50

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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rs760730356

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over