Variant 17-21298479-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_145109.3(MAP2K3):c.116C>A(p.Thr39Lys) variant causes a missense, splice region 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. 2/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 71)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MAP2K3
NM_145109.3 missense, splice_region

Scores

Splicing: ADA: 0.9059

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.27

Variant links:

Genes affected

MAP2K3 (HGNC:6843): (mitogen-activated protein kinase kinase 3) The protein encoded by this gene is a dual specificity protein kinase that belongs to the MAP kinase kinase family. This kinase is activated by mitogenic and environmental stress, and participates in the MAP kinase-mediated signaling cascade. It phosphorylates and thus activates MAPK14/p38-MAPK. This kinase can be activated by insulin, and is necessary for the expression of glucose transporter. Expression of RAS oncogene is found to result in the accumulation of the active form of this kinase, which thus leads to the constitutive activation of MAPK14, and confers oncogenic transformation of primary cells. The inhibition of this kinase is involved in the pathogenesis of Yersina pseudotuberculosis. Multiple alternatively spliced transcript variants that encode distinct isoforms have been reported for this gene. [provided by RefSeq, Jul 2008]

MAP2K3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.300811).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP2K3	NM_145109.3 link	c.116C>A	p.Thr39Lys	missense_variant, splice_region_variant	Exon 2 of 12	ENST00000342679.9	NP_659731.1	P46734-1Q6FI23

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAP2K3	ENST00000342679.9 link	c.116C>A	p.Thr39Lys	missense_variant, splice_region_variant	Exon 2 of 12	1	NM_145109.3	ENSP00000345083.4		P46734-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251404

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135878

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1461872

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727234

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Uncertain

0.038

BayesDel_noAF

Benign

-0.18

CADD

Pathogenic

DANN

Benign

0.92

DEOGEN2

Benign

0.37

T;T;.;.;.

Eigen

Uncertain

0.19

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.91

D;T;T;.;.

M_CAP

Benign

0.022

MetaRNN

Benign

0.30

T;T;T;T;T

MetaSVM

Benign

-0.61

MutationAssessor

Uncertain

2.3

M;.;.;.;.

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-2.0

N;N;N;.;.

REVEL

Benign

0.18

Sift

Benign

0.078

T;T;T;.;.

Sift4G

Benign

0.24

T;T;T;T;T

Polyphen

0.54

P;.;.;.;.

Vest4

0.44

MutPred

0.27

Loss of phosphorylation at T39 (P = 0.003);.;.;.;.;

MVP

0.78

MPC

0.17

ClinPred

0.52

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.16

gMVP

0.42

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.91

dbscSNV1_RF

Pathogenic

0.73

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over