16-29978138-A-G

Position:

• chr16-29978138-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_016151.4(TAOK2):​c.182A>G​(p.Tyr61Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: TAOK2 NM_016151.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.32

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 Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.801

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAOK2	NM_016151.4	c.182A>G	p.Tyr61Cys	missense_variant	3/16	ENST00000308893.9	NP_057235.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAOK2	ENST00000308893.9	c.182A>G	p.Tyr61Cys	missense_variant	3/16	1	NM_016151.4	ENSP00000310094.4
TAOK2	ENST00000543033.5	c.182A>G	p.Tyr61Cys	missense_variant	3/17	1		ENSP00000440336.1
TAOK2	ENST00000279394.7	c.182A>G	p.Tyr61Cys	missense_variant	3/19	1		ENSP00000279394.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461876 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 727244

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.20
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.37	T;.;.
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	D;D;D
M_CAP	Uncertain	0.16	D
MetaRNN	Pathogenic	0.80	D;D;D
MetaSVM	Benign	-0.54	T
MutationAssessor	Benign	0.72	N;N;N
PrimateAI	Pathogenic	0.86	D
PROVEAN	Pathogenic	-7.6	D;D;D
REVEL	Pathogenic	0.70
Sift	Pathogenic	0.0	D;D;D
Sift4G	Uncertain	0.0020	D;D;D
Polyphen		1.0	D;.;D
Vest4		0.67
MutPred		0.60		Loss of methylation at K57 (P = 0.0539);Loss of methylation at K57 (P = 0.0539);Loss of methylation at K57 (P = 0.0539);
MVP		0.83
MPC		2.5
ClinPred		1.0	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.89
gMVP		0.96

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-29989459;