12-118151032-C-A

Position:

• chr12-118151032-C-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_016281.4(TAOK3):​c.2662G>T​(p.Val888Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000479 in 1,460,350 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: TAOK3 NM_016281.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.12

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 Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAOK3	NM_016281.4	c.2662G>T	p.Val888Phe	missense_variant	21/21	ENST00000392533.8	NP_057365.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAOK3	ENST00000392533.8	c.2662G>T	p.Val888Phe	missense_variant	21/21	1	NM_016281.4	ENSP00000376317.3

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1460350 Hom.: 0 Cov.: 36 AF XY: 0.00000826 AC XY: 6 AN XY: 726552

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000540

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

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 14, 2024

The c.2662G>T (p.V888F) alteration is located in exon 21 (coding exon 19) of the TAOK3 gene. This alteration results from a G to T substitution at nucleotide position 2662, causing the valine (V) at amino acid position 888 to be replaced by a phenylalanine (F). 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	0.13
BayesDel_addAF	Uncertain	0.049	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.084	T;T;T;.
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.94	.;D;D;D
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.51	D;D;D;D
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	1.1	L;L;.;.
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-1.7	N;N;D;N
REVEL	Benign	0.16
Sift	Uncertain	0.024	D;D;D;D
Sift4G	Uncertain	0.047	D;D;T;T
Polyphen		0.76	P;P;.;.
Vest4		0.69
MutPred		0.31		Gain of catalytic residue at N886 (P = 0.0055);Gain of catalytic residue at N886 (P = 0.0055);.;.;
MVP		0.34
MPC		1.6
ClinPred		0.64	D
GERP RS		5.3
Varity_R		0.30
gMVP		0.65

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

LitVar

Other links and lift over

dbSNP: rs2034362979; hg19: chr12-118588837;