rs17440433

chr12-118201507-G-Achr12-118201507-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016281.4(TAOK3):c.820-44C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 1,561,866 control chromosomes in the GnomAD database, including 13,614 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.10 (989 hom., cov: 32)
  • Exomes 𝑓: 0.13 (12625 hom.)
• Consequence: TAOK3 NM_016281.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0430

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAOK3	NM_016281.4	c.820-44C>T		intron_variant		ENST00000392533.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAOK3	ENST00000392533.8	c.820-44C>T		intron_variant		1	NM_016281.4	P1

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15414 AN: 152044 Hom.: 988 Cov.: 32

Gnomad AFR AF: 0.0327

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.0989

Gnomad ASJ AF: 0.135

Gnomad EAS AF: 0.0104

Gnomad SAS AF: 0.0578

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.0904

GnomAD3 exomes AF: 0.106 AC: 24641 AN: 231444 Hom.: 1673 AF XY: 0.109 AC XY: 13627 AN XY: 125194

Gnomad AFR exome AF: 0.0295

Gnomad AMR exome AF: 0.0697

Gnomad ASJ exome AF: 0.132

Gnomad EAS exome AF: 0.00333

Gnomad SAS exome AF: 0.0591

Gnomad FIN exome AF: 0.158

Gnomad NFE exome AF: 0.144

Gnomad OTH exome AF: 0.127

GnomAD4 exome AF: 0.130 AC: 182898 AN: 1409704 Hom.: 12625 Cov.: 24 AF XY: 0.128 AC XY: 89842 AN XY: 699928

Gnomad4 AFR exome AF: 0.0304

Gnomad4 AMR exome AF: 0.0723

Gnomad4 ASJ exome AF: 0.129

Gnomad4 EAS exome AF: 0.0280

Gnomad4 SAS exome AF: 0.0584

Gnomad4 FIN exome AF: 0.162

Gnomad4 NFE exome AF: 0.143

Gnomad4 OTH exome AF: 0.121

GnomAD4 genome AF: 0.101 AC: 15410 AN: 152162 Hom.: 989 Cov.: 32 AF XY: 0.100 AC XY: 7437 AN XY: 74394

Gnomad4 AFR AF: 0.0326

Gnomad4 AMR AF: 0.0986

Gnomad4 ASJ AF: 0.135

Gnomad4 EAS AF: 0.0104

Gnomad4 SAS AF: 0.0587

Gnomad4 FIN AF: 0.163

Gnomad4 NFE AF: 0.143

Gnomad4 OTH AF: 0.0913

Alfa AF: 0.0918 Hom.: 210

Bravo AF: 0.0919

Asia WGS AF: 0.0290 AC: 99 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	4.3
Dann	Benign	0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs17440433; hg19: chr12-118639312;