Variant chr17-21300649-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_145109.3(MAP2K3):c.270G>A(p.Met90Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00302 in 1,592,832 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0055 ( 0 hom., cov: 75)

Exomes 𝑓: 0.0028 ( 0 hom. )

Consequence

MAP2K3
NM_145109.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 9.89

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.012894541).

BP6

Variant 17-21300649-G-A is Benign according to our data. Variant chr17-21300649-G-A is described in ClinVar as [Benign]. Clinvar id is 787643.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAP2K3	NM_145109.3 linkuse as main transcript	c.270G>A	p.Met90Ile	missense_variant	4/12	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.270G>A	p.Met90Ile	missense_variant	4/12	1	NM_145109.3	ENSP00000345083	P1	P46734-1

Frequencies

GnomAD3 genomes

AF:

0.00549

AC:

834

AN:

151928

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00121

Gnomad AMI

AF:

0.0155

Gnomad AMR

AF:

0.00157

Gnomad ASJ

AF:

0.00403

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00332

Gnomad FIN

AF:

0.0228

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00687

Gnomad OTH

AF:

0.00478

GnomAD4 exome

AF:

0.00276

AC:

3975

AN:

1440786

Hom.:

Cov.:

AF XY:

0.00283

AC XY:

2029

AN XY:

716462

show subpopulations

Gnomad4 AFR exome

AF:

0.000390

Gnomad4 AMR exome

AF:

0.000503

Gnomad4 ASJ exome

AF:

0.00135

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.00147

Gnomad4 FIN exome

AF:

0.0136

Gnomad4 NFE exome

AF:

0.00264

Gnomad4 OTH exome

AF:

0.00285

GnomAD4 genome

AF:

0.00549

AC:

834

AN:

152046

Hom.:

Cov.:

AF XY:

0.00603

AC XY:

448

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.00120

Gnomad4 AMR

AF:

0.00157

Gnomad4 ASJ

AF:

0.00403

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00332

Gnomad4 FIN

AF:

0.0228

Gnomad4 NFE

AF:

0.00687

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00659

Hom.:

ESP6500AA

AF:

0.00114

AC:

ESP6500EA

AF:

0.00523

AC:

ExAC

AF:

0.00600

AC:

728

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.89

BayesDel_addAF

Pathogenic

0.30

BayesDel_noAF

Pathogenic

0.20

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.29

T;T;.;.;.

Eigen

Uncertain

0.27

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.96

D;D;D;.;.

MetaRNN

Benign

0.013

T;T;T;T;T

MetaSVM

Benign

-0.87

MutationAssessor

Benign

0.12

N;.;.;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.83

PROVEAN

Uncertain

-2.9

D;D;D;.;.

REVEL

Uncertain

0.47

Sift

Benign

0.25

T;D;T;.;.

Sift4G

Benign

0.33

T;T;T;T;T

Polyphen

0.41

B;.;.;.;.

Vest4

0.94

MutPred

0.21

Gain of methylation at K93 (P = 0.0867);.;.;.;.;

MVP

0.68

MPC

0.23

ClinPred

0.036

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.39

gMVP

0.51

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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