Variant chr3-185428711-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PP2BP4_StrongBP6_ModerateBS2

The NM_004721.5(MAP3K13):c.130G>A(p.Glu44Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00463 in 1,614,150 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0041 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0047 ( 22 hom. )

Consequence

MAP3K13
NM_004721.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.94

Variant links:

Genes affected

MAP3K13 (HGNC:6852): (mitogen-activated protein kinase kinase kinase 13) The protein encoded by this gene is a member of serine/threonine protein kinase family. This kinase contains a dual leucine-zipper motif, and has been shown to form dimers/oligomers through its leucine-zipper motif. This kinase can phosphorylate and activate MAPK8/JNK, MAP2K7/MKK7, which suggests a role in the JNK signaling pathway. [provided by RefSeq, Jul 2008]

MAP3K13 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

PP2

Missense variant where missense usually causes diseases, MAP3K13

BP4

Computational evidence support a benign effect (MetaRNN=0.008212924).

BP6

Variant 3-185428711-G-A is Benign according to our data. Variant chr3-185428711-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2654329.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 621 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAP3K13	NM_004721.5 linkuse as main transcript	c.130G>A	p.Glu44Lys	missense_variant	2/14	ENST00000265026.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAP3K13	ENST00000265026.8 linkuse as main transcript	c.130G>A	p.Glu44Lys	missense_variant	2/14	1	NM_004721.5	P1	O43283-1

Frequencies

GnomAD3 genomes

AF:

0.00408

AC:

621

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000796

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.00157

Gnomad ASJ

AF:

0.00894

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00585

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00666

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00389

AC:

976

AN:

251036

Hom.:

AF XY:

0.00383

AC XY:

520

AN XY:

135662

show subpopulations

Gnomad AFR exome

AF:

0.00105

Gnomad AMR exome

AF:

0.00113

Gnomad ASJ exome

AF:

0.00696

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00490

Gnomad NFE exome

AF:

0.00634

Gnomad OTH exome

AF:

0.00375

GnomAD4 exome

AF:

0.00468

AC:

6847

AN:

1461864

Hom.:

Cov.:

AF XY:

0.00469

AC XY:

3409

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.000717

Gnomad4 AMR exome

AF:

0.00119

Gnomad4 ASJ exome

AF:

0.00624

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.00524

Gnomad4 NFE exome

AF:

0.00548

Gnomad4 OTH exome

AF:

0.00364

GnomAD4 genome

AF:

0.00408

AC:

621

AN:

152286

Hom.:

Cov.:

AF XY:

0.00389

AC XY:

290

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.000794

Gnomad4 AMR

AF:

0.00157

Gnomad4 ASJ

AF:

0.00894

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00585

Gnomad4 NFE

AF:

0.00666

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00589

Hom.:

Bravo

AF:

0.00375

TwinsUK

AF:

0.00431

AC:

ALSPAC

AF:

0.00363

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00593

AC:

ExAC

AF:

0.00419

AC:

509

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00469

EpiControl

AF:

0.00391

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

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2022

MAP3K13: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Uncertain

0.98

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.62

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.81

T;.;T;T

M_CAP

Benign

0.024

MetaRNN

Benign

0.0082

T;T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

D;D;D;N;N

PrimateAI

Benign

0.24

PROVEAN

Benign

-1.3

N;N;N;N

REVEL

Benign

0.20

Sift

Benign

0.33

T;T;T;T

Sift4G

Benign

0.30

T;T;T;T

Polyphen

0.0010

.;B;.;B

Vest4

0.14, 0.14

MVP

0.72

MPC

0.11

ClinPred

0.0064

GERP RS

2.6

Varity_R

0.055

gMVP

0.25

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