Variant 17-21300629-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_145109.3(MAP2K3):c.250G>A(p.Ala84Thr) variant causes a missense change. The variant allele was found at a frequency of 0.103 in 979,956 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 0.30 ( 0 hom., cov: 72)

Exomes 𝑓: 0.10 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MAP2K3
NM_145109.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.21

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 Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0021773577).

BP6

Variant 17-21300629-G-A is Benign according to our data. Variant chr17-21300629-G-A is described in ClinVar as [Benign]. Clinvar id is 768847.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.221 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAP2K3	NM_145109.3 linkuse as main transcript	c.250G>A	p.Ala84Thr	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.250G>A	p.Ala84Thr	missense_variant	4/12	1	NM_145109.3	ENSP00000345083	P1	P46734-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

41759

AN:

138360

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.387

Gnomad AMI

AF:

0.368

Gnomad AMR

AF:

0.259

Gnomad ASJ

AF:

0.314

Gnomad EAS

AF:

0.298

Gnomad SAS

AF:

0.270

Gnomad FIN

AF:

0.175

Gnomad MID

AF:

0.271

Gnomad NFE

AF:

0.282

Gnomad OTH

AF:

0.297

GnomAD3 exomes

AF:

0.116

AC:

19510

AN:

167508

Hom.:

AF XY:

0.112

AC XY:

10175

AN XY:

90704

show subpopulations

Gnomad AFR exome

AF:

0.245

Gnomad AMR exome

AF:

0.0683

Gnomad ASJ exome

AF:

0.104

Gnomad EAS exome

AF:

0.124

Gnomad SAS exome

AF:

0.0880

Gnomad FIN exome

AF:

0.0859

Gnomad NFE exome

AF:

0.130

Gnomad OTH exome

AF:

0.107

GnomAD4 exome

AF:

0.103

AC:

100819

AN:

979956

Hom.:

Cov.:

AF XY:

0.106

AC XY:

51699

AN XY:

486604

show subpopulations

Gnomad4 AFR exome

AF:

0.226

Gnomad4 AMR exome

AF:

0.107

Gnomad4 ASJ exome

AF:

0.160

Gnomad4 EAS exome

AF:

0.166

Gnomad4 SAS exome

AF:

0.112

Gnomad4 FIN exome

AF:

0.104

Gnomad4 NFE exome

AF:

0.0933

Gnomad4 OTH exome

AF:

0.127

GnomAD4 genome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.302

AC:

41797

AN:

138468

Hom.:

Cov.:

AF XY:

0.296

AC XY:

20028

AN XY:

67742

show subpopulations

Gnomad4 AFR

AF:

0.387

Gnomad4 AMR

AF:

0.259

Gnomad4 ASJ

AF:

0.314

Gnomad4 EAS

AF:

0.297

Gnomad4 SAS

AF:

0.271

Gnomad4 FIN

AF:

0.175

Gnomad4 NFE

AF:

0.282

Gnomad4 OTH

AF:

0.299

Alfa

AF:

0.255

Hom.:

ExAC

AF:

0.184

AC:

22319

Asia WGS

AF:

0.000577

AC:

AN:

3478

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

Benign

0.066

BayesDel_addAF

Uncertain

0.077

BayesDel_noAF

Benign

-0.13

CADD

Uncertain

DANN

Benign

0.95

DEOGEN2

Benign

0.063

T;T;.;.;.

Eigen

Benign

0.17

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.86

D;T;D;.;.

MetaRNN

Benign

0.0022

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.36

N;.;.;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-0.090

N;N;N;.;.

REVEL

Benign

0.13

Sift

Benign

0.26

T;T;T;.;.

Sift4G

Benign

0.44

T;T;T;T;T

Polyphen

0.87

P;.;.;.;.

Vest4

0.21

MPC

0.13

ClinPred

0.013

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.063

gMVP

0.32

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

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