12-118177317-C-T

Position:

• chr12-118177317-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 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. 14/21 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

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 Uncertain_significance. Variant got 0 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAOK3	NM_016281.4	c.1579G>A	p.Ala527Thr	missense_variant	16/21	ENST00000392533.8	NP_057365.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAOK3	ENST00000392533.8	c.1579G>A	p.Ala527Thr	missense_variant	16/21	1	NM_016281.4	ENSP00000376317.3
TAOK3	ENST00000419821.6	c.1579G>A	p.Ala527Thr	missense_variant	16/21	1		ENSP00000416374.2
TAOK3	ENST00000537952.1	c.199G>A	p.Ala67Thr	missense_variant	3/8	2		ENSP00000443834.1
TAOK3	ENST00000537305.5	n.2260G>A		non_coding_transcript_exon_variant	13/18	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 15, 2024

The c.1579G>A (p.A527T) alteration is located in exon 16 (coding exon 14) of the TAOK3 gene. This alteration results from a G to A substitution at nucleotide position 1579, causing the alanine (A) at amino acid position 527 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;T;.
Eigen	Benign	-0.031
Eigen_PC	Benign	0.14
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.84	.;T;T
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.15	T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.0	M;M;.
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.59	N;N;N
REVEL	Benign	0.088
Sift	Benign	0.50	T;T;T
Sift4G	Benign	0.56	T;T;T
Polyphen		0.0050	B;B;.
Vest4		0.21
MutPred		0.24		Gain of helix (P = 0.0496);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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-118615122;