chr12-118244946-C-G

Variant names:

• chr12-118244946-C-G
• rs428073
• NM_016281.4:c.140G>C

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.140G>C​(p.Ser47Thr) 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. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TAOK3 NM_016281.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.88
• Publications: 55 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=0.21066839).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAOK3	NM_016281.4	c.140G>C	p.Ser47Thr	missense_variant	Exon 4 of 21	ENST00000392533.8	NP_057365.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAOK3	ENST00000392533.8	c.140G>C	p.Ser47Thr	missense_variant	Exon 4 of 21	1	NM_016281.4	ENSP00000376317.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1456310 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 724632

African (AFR) AF: 0.00 AC: 0 AN: 33358

American (AMR) AF: 0.00 AC: 0 AN: 44632

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26004

East Asian (EAS) AF: 0.00 AC: 0 AN: 39596

South Asian (SAS) AF: 0.00 AC: 0 AN: 86144

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53078

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1107638

Other (OTH) AF: 0.00 AC: 0 AN: 60106

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 155815

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	18
DANN	Uncertain	0.97
DEOGEN2	Benign	0.059	T;T;T;T;T;T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.16
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.67	.;T;T;T;T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.21	T;T;T;T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.1	L;L;.;.;.;.
PhyloP100		2.9
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-1.3	N;N;N;N;N;N
REVEL	Benign	0.12
Sift	Benign	0.035	D;D;T;T;D;D
Sift4G	Benign	0.19	T;T;T;T;.;.
Polyphen		0.0	B;B;.;.;.;.
Vest4		0.16
MutPred		0.54		Gain of catalytic residue at T42 (P = 0);Gain of catalytic residue at T42 (P = 0);Gain of catalytic residue at T42 (P = 0);Gain of catalytic residue at T42 (P = 0);Gain of catalytic residue at T42 (P = 0);Gain of catalytic residue at T42 (P = 0);
MVP		0.36
MPC		0.35
ClinPred		0.73	D
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.35
gMVP		0.40
Mutation Taster		=98/2	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

dbSNP: rs428073; hg19: chr12-118682751;