chr12-118177317-C-T

Variant names:

• chr12-118177317-C-T
• NM_016281.4:c.1579G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016281.4(TAOK3):​c.1579G>A​(p.Ala527Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TAOK3 NM_016281.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.26
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1472238).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016281.4. 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
	TAOK3	NM_016281.4	MANE Select	c.1579G>A	p.Ala527Thr	missense	Exon 16 of 21	NP_057365.3
	TAOK3	NM_001346487.2		c.1606G>A	p.Ala536Thr	missense	Exon 16 of 21	NP_001333416.1
	TAOK3	NM_001346488.2		c.1579G>A	p.Ala527Thr	missense	Exon 17 of 22	NP_001333417.1	Q9H2K8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAOK3	ENST00000392533.8	TSL:1 MANE Select	c.1579G>A	p.Ala527Thr	missense	Exon 16 of 21	ENSP00000376317.3	Q9H2K8
	TAOK3	ENST00000419821.6	TSL:1	c.1579G>A	p.Ala527Thr	missense	Exon 16 of 21	ENSP00000416374.2	Q9H2K8
	TAOK3	ENST00000894342.1		c.1579G>A	p.Ala527Thr	missense	Exon 17 of 22	ENSP00000564401.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	22
DANN	Benign	0.95
DEOGEN2	Benign	0.045	T
Eigen	Benign	-0.031
Eigen_PC	Benign	0.14
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		3.3
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.59	N
REVEL	Benign	0.088
Sift	Benign	0.50	T
Sift4G	Benign	0.56	T
Polyphen		0.0050	B
Vest4		0.21
MutPred		0.24		Gain of helix (P = 0.0496)
MVP		0.56
MPC		0.98
ClinPred		0.72	D
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.11
gMVP		0.070
Mutation Taster		=67/33	polymorphism

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

hg19: chr12-118615122;