Variant 17-21298479-C-T 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.116C>T(p.Thr39Ile) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000455 in 1,613,738 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0018 ( 0 hom., cov: 71)

Exomes 𝑓: 0.00032 ( 0 hom. )

Consequence

MAP2K3
NM_145109.3 missense, splice_region

Scores

Splicing: ADA: 0.9561

Clinical Significance

Likely benign criteria provided, single submitter B:1

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:

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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=0.0058155954).

BP6

Variant 17-21298479-C-T is Benign according to our data. Variant chr17-21298479-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 719738.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAP2K3	NM_145109.3 linkuse as main transcript	c.116C>T	p.Thr39Ile	missense_variant, splice_region_variant	2/12	ENST00000342679.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAP2K3	ENST00000342679.9 linkuse as main transcript	c.116C>T	p.Thr39Ile	missense_variant, splice_region_variant	2/12	1	NM_145109.3	P1	P46734-1

Frequencies

GnomAD3 genomes

AF:

0.00180

AC:

274

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00614

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00290

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.000943

AC:

237

AN:

251404

Hom.:

AF XY:

0.000913

AC XY:

124

AN XY:

135878

show subpopulations

Gnomad AFR exome

AF:

0.00784

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00307

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.0000527

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000315

AC:

461

AN:

1461422

Hom.:

Cov.:

AF XY:

0.000325

AC XY:

236

AN XY:

726982

show subpopulations

Gnomad4 AFR exome

AF:

0.00604

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00237

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000225

Gnomad4 OTH exome

AF:

0.000414

GnomAD4 genome

AF:

0.00180

AC:

274

AN:

152316

Hom.:

Cov.:

AF XY:

0.00169

AC XY:

126

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.00612

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00290

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.000308

Hom.:

ESP6500AA

AF:

0.00635

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00113

AC:

137

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Uncertain

0.018

BayesDel_noAF

Benign

-0.21

CADD

Pathogenic

DANN

Benign

0.94

DEOGEN2

Uncertain

0.55

D;T;.;.;.

Eigen

Uncertain

0.24

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.92

D;D;T;.;.

M_CAP

Benign

0.023

MetaRNN

Benign

0.0058

T;T;T;T;T

MetaSVM

Benign

-0.63

MutationAssessor

Uncertain

2.5

M;.;.;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-2.3

N;D;N;.;.

REVEL

Benign

0.19

Sift

Benign

0.099

T;T;T;.;.

Sift4G

Benign

0.11

T;T;T;T;T

Polyphen

0.72

P;.;.;.;.

Vest4

0.47

MVP

0.79

MPC

0.17

ClinPred

0.033

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.12

gMVP

0.29

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.96

dbscSNV1_RF

Benign

0.59

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