Variant 18-50664008-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_002747.4(MAPK4):c.50G>A(p.Gly17Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00172 in 1,613,796 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0018 ( 7 hom. )

Consequence

MAPK4
NM_002747.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.83

Variant links:

Genes affected

MAPK4 (HGNC:6878): (mitogen-activated protein kinase 4) Mitogen-activated protein kinase 4 is a member of the mitogen-activated protein kinase family. Tyrosine kinase growth factor receptors activate mitogen-activated protein kinases which then translocate into the nucleus and phosphorylate nuclear targets. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]

MAPK4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.055694282).

BS2

High AC in GnomAd4 at 175 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAPK4	NM_002747.4 link	c.50G>A	p.Gly17Asp	missense_variant	2/6	ENST00000400384.7	NP_002738.2	P31152

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MAPK4	ENST00000400384.7 link	c.50G>A	p.Gly17Asp	missense_variant	2/6	1	NM_002747.4	ENSP00000383234.1	P31152
MAPK4	ENST00000588540.1 link	c.50G>A	p.Gly17Asp	missense_variant	2/3	1		ENSP00000465661.1	K7EN18
MAPK4	ENST00000592595.5 link	c.50G>A	p.Gly17Asp	missense_variant	2/4	1		ENSP00000466233.1	K7ELV1
MAPK4	ENST00000540640.3 link	c.-87-51071G>A		intron_variant		2		ENSP00000439231.1	B4DEW2

Frequencies

GnomAD3 genomes

AF:

0.00115

AC:

175

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000507

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00204

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.00105

AC:

262

AN:

249216

Hom.:

AF XY:

0.000998

AC XY:

135

AN XY:

135224

show subpopulations

Gnomad AFR exome

AF:

0.000323

Gnomad AMR exome

AF:

0.000927

Gnomad ASJ exome

AF:

0.0000994

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000948

Gnomad FIN exome

AF:

0.000282

Gnomad NFE exome

AF:

0.00165

Gnomad OTH exome

AF:

0.000330

GnomAD4 exome

AF:

0.00178

AC:

2599

AN:

1461474

Hom.:

Cov.:

AF XY:

0.00173

AC XY:

1256

AN XY:

727026

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.000872

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000869

Gnomad4 FIN exome

AF:

0.000321

Gnomad4 NFE exome

AF:

0.00212

Gnomad4 OTH exome

AF:

0.00177

GnomAD4 genome

AF:

0.00115

AC:

175

AN:

152322

Hom.:

Cov.:

AF XY:

0.00111

AC XY:

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.000505

Gnomad4 AMR

AF:

0.000588

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00204

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.00167

Hom.:

Bravo

AF:

0.00123

TwinsUK

AF:

0.00270

AC:

ALSPAC

AF:

0.00259

AC:

ESP6500AA

AF:

0.000487

AC:

ESP6500EA

AF:

0.00286

AC:

ExAC

AF:

0.00109

AC:

132

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00164

EpiControl

AF:

0.00172

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 11, 2024

The c.50G>A (p.G17D) alteration is located in exon 2 (coding exon 1) of the MAPK4 gene. This alteration results from a G to A substitution at nucleotide position 50, causing the glycine (G) at amino acid position 17 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.50

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.14

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.21

T;T;.

Eigen

Uncertain

0.20

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.73

T;T;T

M_CAP

Benign

0.042

MetaRNN

Benign

0.056

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.3

L;.;.

PrimateAI

Uncertain

0.66

PROVEAN

Uncertain

-4.1

D;.;.

REVEL

Benign

0.18

Sift

Benign

0.050

D;.;.

Sift4G

Benign

0.27

T;T;T

Polyphen

0.83

P;.;.

Vest4

0.54

MVP

0.89

MPC

1.8

ClinPred

0.025

GERP RS

5.7

Varity_R

0.58

gMVP

0.64

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