rs4583255

Positions:

• chr16-29977620-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_016151.4(TAOK2):​c.-35-118A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.427 in 964,436 control chromosomes in the GnomAD database, including 91,467 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 0.36 (10834 hom., cov: 31)
  • Exomes 𝑓: 0.44 (80633 hom.)
• Consequence: TAOK2 NM_016151.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.18

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.473 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAOK2	NM_016151.4	c.-35-118A>G		intron_variant		ENST00000308893.9	NP_057235.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAOK2	ENST00000308893.9	c.-35-118A>G		intron_variant		1	NM_016151.4	ENSP00000310094
TAOK2	ENST00000279394.7	c.-35-118A>G		intron_variant		1		ENSP00000279394	P1
TAOK2	ENST00000543033.5	c.-35-118A>G		intron_variant		1		ENSP00000440336

Frequencies

GnomAD3 genomes AF: 0.360 AC: 54582 AN: 151790 Hom.: 10836 Cov.: 31

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.474

Gnomad AMR AF: 0.344

Gnomad ASJ AF: 0.439

Gnomad EAS AF: 0.399

Gnomad SAS AF: 0.489

Gnomad FIN AF: 0.405

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.448

Gnomad OTH AF: 0.353

GnomAD4 exome AF: 0.440 AC: 357590 AN: 812528 Hom.: 80633 AF XY: 0.442 AC XY: 179785 AN XY: 406972

Gnomad4 AFR exome AF: 0.171

Gnomad4 AMR exome AF: 0.331

Gnomad4 ASJ exome AF: 0.449

Gnomad4 EAS exome AF: 0.357

Gnomad4 SAS exome AF: 0.499

Gnomad4 FIN exome AF: 0.398

Gnomad4 NFE exome AF: 0.455

Gnomad4 OTH exome AF: 0.425

GnomAD4 genome AF: 0.359 AC: 54569 AN: 151908 Hom.: 10834 Cov.: 31 AF XY: 0.360 AC XY: 26698 AN XY: 74236

Gnomad4 AFR AF: 0.179

Gnomad4 AMR AF: 0.343

Gnomad4 ASJ AF: 0.439

Gnomad4 EAS AF: 0.399

Gnomad4 SAS AF: 0.489

Gnomad4 FIN AF: 0.405

Gnomad4 NFE AF: 0.448

Gnomad4 OTH AF: 0.351

Alfa AF: 0.423 Hom.: 9314

Bravo AF: 0.340

Asia WGS AF: 0.351 AC: 1226 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	17
DANN	Benign	0.80

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs4583255; hg19: chr16-29988941; COSMIC: COSV54242544; COSMIC: COSV54242544;