rs4583255

Variant names:

• chr16-29977620-A-G
• rs4583255
• NM_016151.4:c.-35-118A>G

Your query was ambiguous. Multiple possible variants found:

• chr16-29977620-A-G
• chr16-29977620-A-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 18 publications found

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]

TAOK2 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia
• autism spectrum disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• immunodeficiency disease

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics
• inborn error of immunity

  Inheritance: AR Classification: LIMITED Submitted by: PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016151.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAOK2	NM_016151.4	MANE Select	c.-35-118A>G		intron	N/A	NP_057235.2
	TAOK2	NM_001252043.2		c.-35-118A>G		intron	N/A	NP_001238972.1	Q9UL54-4
	TAOK2	NM_004783.4		c.-35-118A>G		intron	N/A	NP_004774.1	Q9UL54-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAOK2	ENST00000308893.9	TSL:1 MANE Select	c.-35-118A>G		intron	N/A	ENSP00000310094.4	Q9UL54-1
	TAOK2	ENST00000543033.5	TSL:1	c.-35-118A>G		intron	N/A	ENSP00000440336.1	Q9UL54-4
	TAOK2	ENST00000279394.7	TSL:1	c.-35-118A>G		intron	N/A	ENSP00000279394.3	Q9UL54-2

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

African (AFR) AF: 0.171 AC: 3272 AN: 19100

American (AMR) AF: 0.331 AC: 6316 AN: 19058

Ashkenazi Jewish (ASJ) AF: 0.449 AC: 6997 AN: 15592

East Asian (EAS) AF: 0.357 AC: 11627 AN: 32586

South Asian (SAS) AF: 0.499 AC: 25375 AN: 50818

European-Finnish (FIN) AF: 0.398 AC: 12402 AN: 31128

Middle Eastern (MID) AF: 0.366 AC: 973 AN: 2660

European-Non Finnish (NFE) AF: 0.455 AC: 274601 AN: 603870

Other (OTH) AF: 0.425 AC: 16027 AN: 37716

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

African (AFR) AF: 0.179 AC: 7427 AN: 41458

American (AMR) AF: 0.343 AC: 5245 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.439 AC: 1523 AN: 3470

East Asian (EAS) AF: 0.399 AC: 2053 AN: 5148

South Asian (SAS) AF: 0.489 AC: 2353 AN: 4812

European-Finnish (FIN) AF: 0.405 AC: 4266 AN: 10542

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.448 AC: 30420 AN: 67898

Other (OTH) AF: 0.351 AC: 740 AN: 2110

Alfa AF: 0.418 Hom.: 10922

Bravo AF: 0.340

Asia WGS AF: 0.351 AC: 1226 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	17
DANN	Benign	0.80
PhyloP100		1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4583255; hg19: chr16-29988941; COSMIC: COSV54242544; COSMIC: COSV54242544;