chr12-118371498-A-G

Variant names:

• chr12-118371498-A-G
• rs514826
• NM_016281.4:c.-194+1150T>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+1150T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.695 in 151,566 control chromosomes in the GnomAD database, including 36,804 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 0.70 (36804 hom., cov: 30)
• Consequence: TAOK3 NM_016281.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.300
• Publications: 1 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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.731 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAOK3	NM_016281.4	c.-194+1150T>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+1150T>C		intron_variant	Intron 1 of 20	1	NM_016281.4	ENSP00000376317.3
TAOK3	ENST00000542532.5	c.-292+1150T>C		intron_variant	Intron 1 of 3	2		ENSP00000441071.1
TAOK3	ENST00000542692.1	n.246+1150T>C		intron_variant	Intron 1 of 3	3

Frequencies

GnomAD3 genomes AF: 0.695 AC: 105280 AN: 151448 Hom.: 36760 Cov.: 30

Gnomad AFR AF: 0.738

Gnomad AMI AF: 0.437

Gnomad AMR AF: 0.736

Gnomad ASJ AF: 0.739

Gnomad EAS AF: 0.707

Gnomad SAS AF: 0.751

Gnomad FIN AF: 0.667

Gnomad MID AF: 0.625

Gnomad NFE AF: 0.662

Gnomad OTH AF: 0.680

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

GnomAD4 genome AF: 0.695 AC: 105371 AN: 151566 Hom.: 36804 Cov.: 30 AF XY: 0.697 AC XY: 51613 AN XY: 74058

African (AFR) AF: 0.738 AC: 30521 AN: 41364

American (AMR) AF: 0.736 AC: 11230 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.739 AC: 2563 AN: 3466

East Asian (EAS) AF: 0.707 AC: 3588 AN: 5074

South Asian (SAS) AF: 0.752 AC: 3608 AN: 4800

European-Finnish (FIN) AF: 0.667 AC: 7010 AN: 10506

Middle Eastern (MID) AF: 0.610 AC: 177 AN: 290

European-Non Finnish (NFE) AF: 0.662 AC: 44849 AN: 67792

Other (OTH) AF: 0.679 AC: 1429 AN: 2106

Alfa AF: 0.676 Hom.: 56657

Bravo AF: 0.698

Asia WGS AF: 0.708 AC: 2464 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.2
DANN	Benign	0.45
PhyloP100		-0.30
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs514826; hg19: chr12-118809303;