Variant 17-21302249-T-C 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.506T>C(p.Ile169Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000761 in 1,604,920 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., cov: 66)

Exomes 𝑓: 0.00071 ( 0 hom. )

Consequence

MAP2K3
NM_145109.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.87

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=0.06319314).

BP6

Variant 17-21302249-T-C is Benign according to our data. Variant chr17-21302249-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 717560.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.506T>C	p.Ile169Thr	missense_variant	6/12	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.506T>C	p.Ile169Thr	missense_variant	6/12	1	NM_145109.3	ENSP00000345083	P1	P46734-1

Frequencies

GnomAD3 genomes

AF:

0.00129

AC:

194

AN:

150356

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000148

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000199

Gnomad ASJ

AF:

0.000289

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00299

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00227

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000706

AC:

1027

AN:

1454456

Hom.:

Cov.:

AF XY:

0.000778

AC XY:

563

AN XY:

723664

show subpopulations

Gnomad4 AFR exome

AF:

0.0000900

Gnomad4 AMR exome

AF:

0.000135

Gnomad4 ASJ exome

AF:

0.000269

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00239

Gnomad4 NFE exome

AF:

0.000760

Gnomad4 OTH exome

AF:

0.000667

GnomAD4 genome

AF:

0.00129

AC:

194

AN:

150464

Hom.:

Cov.:

AF XY:

0.00128

AC XY:

AN XY:

73482

show subpopulations

Gnomad4 AFR

AF:

0.000147

Gnomad4 AMR

AF:

0.000198

Gnomad4 ASJ

AF:

0.000289

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00299

Gnomad4 NFE

AF:

0.00227

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00197

Hom.:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00163

AC:

ExAC

AF:

0.00220

AC:

267

EpiCase

AF:

0.000876

EpiControl

AF:

0.000595

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

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.52

BayesDel_addAF

Pathogenic

0.41

BayesDel_noAF

Pathogenic

0.35

CADD

Pathogenic

DANN

Benign

0.95

DEOGEN2

Benign

0.37

T;T;.;.;.

Eigen

Uncertain

0.64

Eigen_PC

Uncertain

0.62

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.92

D;D;D;.;.

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.063

T;T;T;T;T

MetaSVM

Uncertain

-0.25

MutationAssessor

Uncertain

2.7

M;.;.;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.78

PROVEAN

Pathogenic

-4.6

D;.;D;.;.

REVEL

Uncertain

0.64

Sift

Uncertain

0.017

D;.;D;.;.

Sift4G

Uncertain

0.017

D;T;D;D;D

Polyphen

0.51

P;.;.;.;.

Vest4

0.87

MVP

0.98

MPC

0.24

ClinPred

0.10

GERP RS

5.2

Varity_R

0.34

gMVP

0.75

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