chr12-118244946-C-T

Variant names:

• chr12-118244946-C-T
• rs428073
• NM_016281.4:c.140G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.88
• Publications: 55 publications found

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]

ACMG classification

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	c.140G>A	p.Ser47Asn	missense_variant	Exon 4 of 21	ENST00000392533.8	NP_057365.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAOK3	ENST00000392533.8	c.140G>A	p.Ser47Asn	missense_variant	Exon 4 of 21	1	NM_016281.4	ENSP00000376317.3

Frequencies

GnomAD3 genomes AF: 0.716 AC: 108790 AN: 151924 Hom.: 39029 Cov.: 32

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

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.: 31 AF XY: 0.697 AC XY: 504020 AN XY: 722758

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

GnomAD4 genome AF: 0.716 AC: 108883 AN: 152042 Hom.: 39072 Cov.: 32 AF XY: 0.718 AC XY: 53330 AN XY: 74294

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

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	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	14
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	N
LIST_S2	Benign	0.28	.;T;T;T;T;T
MetaRNN	Benign	0.0000014	T;T;T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.29	N;N;.;.;.;.
PhyloP100		2.9
PrimateAI	Uncertain	0.58	T
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	T
GERP RS		5.1
Varity_R		0.22
gMVP		0.25
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs428073; hg19: chr12-118682751; COSMIC: COSV62401637; COSMIC: COSV62401637;