Variant chr17-21298879-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_145109.3(MAP2K3):c.118C>A(p.Pro40Thr) variant causes a missense, splice region change. 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 Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.50 ( 1 hom., cov: 62)

Exomes 𝑓: 0.50 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

MAP2K3
NM_145109.3 missense, splice_region

Scores

Splicing: ADA: 0.004856

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 7.19

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0034868717).

BP6

Variant 17-21298879-C-A is Benign according to our data. Variant chr17-21298879-C-A is described in ClinVar as [Benign]. Clinvar id is 768842.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAP2K3	NM_145109.3 linkuse as main transcript	c.118C>A	p.Pro40Thr	missense_variant, splice_region_variant	3/12	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.118C>A	p.Pro40Thr	missense_variant, splice_region_variant	3/12	1	NM_145109.3	ENSP00000345083	P1	P46734-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

76076

AN:

152160

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:

0.500

AC:

729289

AN:

1458886

Hom.:

Cov.:

AF XY:

0.500

AC XY:

362875

AN XY:

725884

show subpopulations

Gnomad4 AFR exome

AF:

0.500

Gnomad4 AMR exome

AF:

0.500

Gnomad4 ASJ exome

AF:

0.500

Gnomad4 EAS exome

AF:

0.500

Gnomad4 SAS exome

AF:

0.500

Gnomad4 FIN exome

AF:

0.500

Gnomad4 NFE exome

AF:

0.500

Gnomad4 OTH exome

AF:

0.500

GnomAD4 genome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.500

AC:

76135

AN:

152278

Hom.:

Cov.:

AF XY:

0.500

AC XY:

37233

AN XY:

74470

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:

0.500

Hom.:

ExAC

AF:

0.500

AC:

60691

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 04, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.37

BayesDel_addAF

Uncertain

0.062

BayesDel_noAF

Benign

-0.15

CADD

Uncertain

DANN

Benign

0.94

DEOGEN2

Uncertain

0.60

D;T;.;.;.

Eigen

Benign

0.14

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.71

T;T;T;.;.

MetaRNN

Benign

0.0035

T;T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Pathogenic

3.0

M;.;.;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.57

PROVEAN

Uncertain

-3.2

D;D;D;.;.

REVEL

Uncertain

0.36

Sift

Benign

0.039

D;D;D;.;.

Sift4G

Benign

0.24

T;T;T;T;T

Polyphen

0.73

P;.;.;.;.

Vest4

0.34

MPC

0.52

ClinPred

0.056

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.13

gMVP

0.37

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0049

dbscSNV1_RF

Benign

0.19

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