Variant 17-21300880-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BP4_Strong

The NM_145109.3(MAP2K3):c.286C>T(p.Arg96Trp) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.50 ( 0 hom., cov: 67)

Exomes 𝑓: 0.50 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MAP2K3
NM_145109.3 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 4.72

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 Likely_benign. Variant got -3 ACMG points.

PP3

Multiple lines of computational evidence support a deleterious effect 6: AlphaMissense, BayesDel_addAF, BayesDel_noAF, Cadd, PrimateAI, PROVEAN [when max_spliceai, FATHMM_MKL, MetaRNN, MutationTaster was below the threshold]

BP4

Computational evidence support a benign effect (MetaRNN=0.0043037534).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAP2K3	NM_145109.3 linkuse as main transcript	c.286C>T	p.Arg96Trp	missense_variant	5/12	ENST00000342679.9	NP_659731.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAP2K3	ENST00000342679.9 linkuse as main transcript	c.286C>T	p.Arg96Trp	missense_variant	5/12	1	NM_145109.3	ENSP00000345083	P1	P46734-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

76153

AN:

152306

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.500

Gnomad AMI

AF:

0.500

Gnomad AMR

AF:

0.500

Gnomad ASJ

AF:

0.500

Gnomad EAS

AF:

0.500

Gnomad SAS

AF:

0.500

Gnomad FIN

AF:

0.500

Gnomad MID

AF:

0.500

Gnomad NFE

AF:

0.500

Gnomad OTH

AF:

0.500

GnomAD4 exome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.498

AC:

695652

AN:

1395920

Hom.:

Cov.:

105

AF XY:

0.499

AC XY:

347436

AN XY:

696906

show subpopulations

Gnomad4 AFR exome

AF:

0.498

Gnomad4 AMR exome

AF:

0.500

Gnomad4 ASJ exome

AF:

0.499

Gnomad4 EAS exome

AF:

0.500

Gnomad4 SAS exome

AF:

0.499

Gnomad4 FIN exome

AF:

0.500

Gnomad4 NFE exome

AF:

0.498

Gnomad4 OTH exome

AF:

0.499

GnomAD4 genome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.500

AC:

76212

AN:

152424

Hom.:

Cov.:

AF XY:

0.500

AC XY:

37271

AN XY:

74542

show subpopulations

Gnomad4 AFR

AF:

0.500

Gnomad4 AMR

AF:

0.500

Gnomad4 ASJ

AF:

0.500

Gnomad4 EAS

AF:

0.500

Gnomad4 SAS

AF:

0.500

Gnomad4 FIN

AF:

0.500

Gnomad4 NFE

AF:

0.500

Gnomad4 OTH

AF:

0.500

Alfa

AF:

0.493

Hom.:

ExAC

AF:

0.500

AC:

60660

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Hepatocellular carcinoma

Pathogenic:1

Pathogenic, no assertion criteria provided

research

Arun Kumar Laboratory, Indian Institute of Science

Jun 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.91

BayesDel_addAF

Pathogenic

0.35

BayesDel_noAF

Pathogenic

0.26

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.40

T;T;.;.;.

Eigen

Uncertain

0.66

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Uncertain

0.82

LIST_S2

Uncertain

0.91

D;D;D;.;.

MetaRNN

Benign

0.0043

T;T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Uncertain

2.9

M;.;.;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.82

PROVEAN

Pathogenic

-4.9

D;D;D;.;.

REVEL

Uncertain

0.38

Sift

Pathogenic

0.0

D;D;D;.;.

Sift4G

Uncertain

0.043

D;D;T;T;T

Polyphen

1.0

D;.;.;.;.

Vest4

0.70

MPC

0.61

ClinPred

0.038

GERP RS

5.1

Varity_R

0.88

gMVP

0.72

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over