Genetic Variant NM_016281.4:c.140G>A (chr12-118244946-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_016281.4(TAOK3):c.140G>A(p.Ser47Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.699 in 1,604,326 control chromosomes in the GnomAD database, including 393,646 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.72 ( 39072 hom., cov: 32)

Exomes 𝑓: 0.70 ( 354574 hom. )

Consequence

TAOK3
NM_016281.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.88

Publications

55 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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.4425425E-6).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.738 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAOK3	NM_016281.4 link	c.140G>A	p.Ser47Asn	missense_variant	Exon 4 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.140G>A	p.Ser47Asn	missense_variant	Exon 4 of 21	1	NM_016281.4	ENSP00000376317.3		Q9H2K8

Frequencies

GnomAD3 genomes

AF:

0.716

AC:

108790

AN:

151924

Hom.:

39029

Cov.:

show subpopulations

Gnomad AFR

AF:

0.745

Gnomad AMI

AF:

0.641

Gnomad AMR

AF:

0.744

Gnomad ASJ

AF:

0.723

Gnomad EAS

AF:

0.708

Gnomad SAS

AF:

0.756

Gnomad FIN

AF:

0.702

Gnomad MID

AF:

0.595

Gnomad NFE

AF:

0.694

Gnomad OTH

AF:

0.689

GnomAD2 exomes

AF:

0.716

AC:

179471

AN:

250660

AF XY:

0.711

show subpopulations

Gnomad AFR exome

AF:

0.748

Gnomad AMR exome

AF:

0.769

Gnomad ASJ exome

AF:

0.705

Gnomad EAS exome

AF:

0.728

Gnomad FIN exome

AF:

0.703

Gnomad NFE exome

AF:

0.690

Gnomad OTH exome

AF:

0.703

GnomAD4 exome

AF:

0.698

AC:

1013193

AN:

1452284

Hom.:

354574

Cov.:

AF XY:

0.697

AC XY:

504020

AN XY:

722758

show subpopulations

African (AFR)

AF:

0.753

AC:

25076

AN:

33294

American (AMR)

AF:

0.765

AC:

34086

AN:

44582

Ashkenazi Jewish (ASJ)

AF:

0.717

AC:

18639

AN:

25980

East Asian (EAS)

AF:

0.657

AC:

25968

AN:

39528

South Asian (SAS)

AF:

0.743

AC:

63916

AN:

86020

European-Finnish (FIN)

AF:

0.699

AC:

37074

AN:

53002

Middle Eastern (MID)

AF:

0.594

AC:

3413

AN:

5748

European-Non Finnish (NFE)

AF:

0.691

AC:

762693

AN:

1104158

Other (OTH)

AF:

0.706

AC:

42328

AN:

59972

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.452

Heterozygous variant carriers

13704

27409

41113

54818

68522

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19488

38976

58464

77952

97440

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.716

AC:

108883

AN:

152042

Hom.:

39072

Cov.:

AF XY:

0.718

AC XY:

53330

AN XY:

74294

show subpopulations

African (AFR)

AF:

0.745

AC:

30883

AN:

41462

American (AMR)

AF:

0.744

AC:

11361

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.723

AC:

2511

AN:

3472

East Asian (EAS)

AF:

0.708

AC:

3662

AN:

5174

South Asian (SAS)

AF:

0.757

AC:

3641

AN:

4812

European-Finnish (FIN)

AF:

0.702

AC:

7406

AN:

10550

Middle Eastern (MID)

AF:

0.588

AC:

173

AN:

294

European-Non Finnish (NFE)

AF:

0.694

AC:

47213

AN:

67982

Other (OTH)

AF:

0.687

AC:

1448

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1547

3095

4642

6190

7737

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

842

1684

2526

3368

4210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.698

Hom.:

155815

Bravo

AF:

0.718

TwinsUK

AF:

0.691

AC:

2561

ALSPAC

AF:

0.684

AC:

2637

ESP6500AA

AF:

0.747

AC:

3290

ESP6500EA

AF:

0.693

AC:

5957

ExAC

AF:

0.714

AC:

86683

Asia WGS

AF:

0.706

AC:

2457

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.050

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Benign

0.71

DEOGEN2

Benign

0.021

T;T;T;T;T;T

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.45

FATHMM_MKL

Benign

0.098

LIST_S2

Benign

0.28

.;T;T;T;T;T

MetaRNN

Benign

0.0000014

T;T;T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-0.29

N;N;.;.;.;.

PhyloP100

2.9

PrimateAI

Uncertain

0.58

PROVEAN

Benign

2.0

N;N;N;N;N;N

REVEL

Benign

0.072

Sift

Benign

1.0

T;T;T;T;T;T

Sift4G

Benign

1.0

T;T;T;T;.;.

Polyphen

0.0

B;B;.;.;.;.

Vest4

0.029

MPC

0.36

ClinPred

0.0025

GERP RS

5.1

Varity_R

0.22

gMVP

0.25

Mutation Taster

=99/1

polymorphism (auto)

(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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over