Variant 16-30123167-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_002746.3(MAPK3):c.43C>T(p.Arg15Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000662 in 1,420,482 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000087 ( 1 hom., cov: 28)

Exomes 𝑓: 0.000064 ( 1 hom. )

Consequence

MAPK3
NM_002746.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.558

Variant links:

Genes affected

MAPK3 (HGNC:6877): (mitogen-activated protein kinase 3) The protein encoded by this gene is a member of the MAP kinase family. MAP kinases, also known as extracellular signal-regulated kinases (ERKs), act in a signaling cascade that regulates various cellular processes such as proliferation, differentiation, and cell cycle progression in response to a variety of extracellular signals. This kinase is activated by upstream kinases, resulting in its translocation to the nucleus where it phosphorylates nuclear targets. Alternatively spliced transcript variants encoding different protein isoforms have been described. [provided by RefSeq, Jul 2008]

MAPK3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.013619661).

BP6

Variant 16-30123167-G-A is Benign according to our data. Variant chr16-30123167-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 720009.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd at 13 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
MAPK3	NM_002746.3 linkuse as main transcript	c.43C>T	p.Arg15Cys	missense_variant	1/9	ENST00000263025.9
MAPK3	NM_001040056.3 linkuse as main transcript	c.43C>T	p.Arg15Cys	missense_variant	1/7
MAPK3	NM_001109891.2 linkuse as main transcript	c.43C>T	p.Arg15Cys	missense_variant	1/8
MAPK3	XR_243293.2 linkuse as main transcript	n.54C>T		non_coding_transcript_exon_variant	1/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAPK3	ENST00000263025.9 linkuse as main transcript	c.43C>T	p.Arg15Cys	missense_variant	1/9	1	NM_002746.3	P1	P27361-1

Frequencies

GnomAD3 genomes

AF:

0.0000873

AC:

AN:

148938

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000797

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000150

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000606

AC:

AN:

89108

Hom.:

AF XY:

0.000341

AC XY:

AN XY:

49890

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00393

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000637

AC:

AN:

1271444

Hom.:

Cov.:

AF XY:

0.0000510

AC XY:

AN XY:

627266

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00294

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000300

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000872

AC:

AN:

149038

Hom.:

Cov.:

AF XY:

0.0000549

AC XY:

AN XY:

72816

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000796

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000150

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000262

Hom.:

Bravo

AF:

0.000246

ExAC

AF:

0.000301

AC:

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

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.27

Cadd

Uncertain

Dann

Uncertain

0.99

DEOGEN2

Benign

0.31

T;.;.;.

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.38

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.69

T;T;.;T

M_CAP

Pathogenic

0.98

MetaRNN

Benign

0.014

T;T;T;T

MetaSVM

Benign

-0.70

MutationAssessor

Benign

0.0

N;N;N;N

MutationTaster

Benign

0.87

D;D;D;D;D

PrimateAI

Pathogenic

0.94

PROVEAN

Benign

-0.52

N;N;N;N

REVEL

Uncertain

0.34

Sift

Benign

0.037

D;D;D;D

Sift4G

Uncertain

0.053

T;T;T;T

Polyphen

0.0

B;B;B;B

Vest4

0.28

MVP

0.93

MPC

1.6

ClinPred

0.15

GERP RS

2.9

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.1

Varity_R

0.13

gMVP

0.46

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