rs2784

Variant names:

• chr12-118311745-T-C
• rs2784
• NM_016281.4:c.-193-44986A>G

Variant summary

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

The NM_016281.4(TAOK3):​c.-193-44986A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0954 in 152,244 control chromosomes in the GnomAD database, including 869 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 0.095 (869 hom., cov: 33)
• Consequence: TAOK3 NM_016281.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.06
• Publications: 6 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAOK3	NM_016281.4	c.-193-44986A>G		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.-193-44986A>G		intron_variant	Intron 1 of 20	1	NM_016281.4	ENSP00000376317.3

Frequencies

GnomAD3 genomes AF: 0.0955 AC: 14522 AN: 152126 Hom.: 868 Cov.: 33

Gnomad AFR AF: 0.0310

Gnomad AMI AF: 0.0626

Gnomad AMR AF: 0.0906

Gnomad ASJ AF: 0.135

Gnomad EAS AF: 0.0102

Gnomad SAS AF: 0.0516

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.0795

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

GnomAD4 genome AF: 0.0954 AC: 14518 AN: 152244 Hom.: 869 Cov.: 33 AF XY: 0.0949 AC XY: 7067 AN XY: 74460

African (AFR) AF: 0.0309 AC: 1286 AN: 41562

American (AMR) AF: 0.0903 AC: 1382 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.135 AC: 467 AN: 3466

East Asian (EAS) AF: 0.0102 AC: 53 AN: 5182

South Asian (SAS) AF: 0.0522 AC: 252 AN: 4826

European-Finnish (FIN) AF: 0.164 AC: 1732 AN: 10576

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.134 AC: 9081 AN: 68014

Other (OTH) AF: 0.0806 AC: 170 AN: 2110

Alfa AF: 0.113 Hom.: 179

Bravo AF: 0.0855

Asia WGS AF: 0.0260 AC: 91 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.79
DANN	Benign	0.71
PhyloP100		-2.1
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: rs2784; hg19: chr12-118749550; COSMIC: COSV66825650;