12-118330623-A-G

Variant names:

• chr12-118330623-A-G
• rs575121
• NM_016281.4:c.-194+42025T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016281.4(TAOK3):​c.-194+42025T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.385 in 151,720 control chromosomes in the GnomAD database, including 11,713 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.38 (11713 hom., cov: 30)
• Consequence: TAOK3 NM_016281.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.458
• Publications: 3 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.436 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAOK3	NM_016281.4	c.-194+42025T>C		intron_variant	Intron 1 of 20	ENST00000392533.8	NP_057365.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAOK3	ENST00000392533.8	c.-194+42025T>C		intron_variant	Intron 1 of 20	1	NM_016281.4	ENSP00000376317.3

Frequencies

GnomAD3 genomes AF: 0.385 AC: 58393 AN: 151602 Hom.: 11710 Cov.: 30

Gnomad AFR AF: 0.273

Gnomad AMI AF: 0.462

Gnomad AMR AF: 0.397

Gnomad ASJ AF: 0.412

Gnomad EAS AF: 0.380

Gnomad SAS AF: 0.406

Gnomad FIN AF: 0.433

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.440

Gnomad OTH AF: 0.393

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.385 AC: 58410 AN: 151720 Hom.: 11713 Cov.: 30 AF XY: 0.385 AC XY: 28545 AN XY: 74152

African (AFR) AF: 0.272 AC: 11260 AN: 41378

American (AMR) AF: 0.397 AC: 6035 AN: 15200

Ashkenazi Jewish (ASJ) AF: 0.412 AC: 1430 AN: 3470

East Asian (EAS) AF: 0.379 AC: 1961 AN: 5168

South Asian (SAS) AF: 0.407 AC: 1958 AN: 4816

European-Finnish (FIN) AF: 0.433 AC: 4545 AN: 10486

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.440 AC: 29888 AN: 67896

Other (OTH) AF: 0.390 AC: 822 AN: 2106

Alfa AF: 0.422 Hom.: 3131

Bravo AF: 0.380

Asia WGS AF: 0.382 AC: 1329 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.4
DANN	Benign	0.68
PhyloP100		-0.46
Mutation Taster		=100/0	polymorphism (auto)

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: rs575121; hg19: chr12-118768428;