Variant rs55776345 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_002754.5(MAPK13):c.122C>T(p.Ser41Leu) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0119 in 1,611,930 control chromosomes in the GnomAD database, including 144 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.0090 ( 14 hom., cov: 32)

Exomes 𝑓: 0.012 ( 130 hom. )

Consequence

MAPK13
NM_002754.5 missense, splice_region

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.89

Variant links:

Genes affected

MAPK13 (HGNC:6875): (mitogen-activated protein kinase 13) This gene encodes a member of the mitogen-activated protein (MAP) kinase family. MAP kinases act as an integration point for multiple biochemical signals, and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation and development. The encoded protein is a p38 MAP kinase and is activated by proinflammatory cytokines and cellular stress. Substrates of the encoded protein include the transcription factor ATF2 and the microtubule dynamics regulator stathmin. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Jul 2012]

MAPK13 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011768967).

BP6

Variant 6-36131273-C-T is Benign according to our data. Variant chr6-36131273-C-T is described in ClinVar as [Benign]. Clinvar id is 775077.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAPK13	NM_002754.5 link	c.122C>T	p.Ser41Leu	missense_variant, splice_region_variant	Exon 2 of 12	ENST00000211287.9	NP_002745.1	O15264-1A0A024RD04
MAPK13	NR_072996.2 link	n.192C>T		splice_region_variant, non_coding_transcript_exon_variant	Exon 2 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAPK13	ENST00000211287.9 link	c.122C>T	p.Ser41Leu	missense_variant, splice_region_variant	Exon 2 of 12	1	NM_002754.5	ENSP00000211287.4		O15264-1

Frequencies

GnomAD3 genomes

AF:

0.00897

AC:

1365

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00198

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00667

Gnomad ASJ

AF:

0.0135

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.0106

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0146

Gnomad OTH

AF:

0.00860

GnomAD3 exomes

AF:

0.00953

AC:

2373

AN:

248876

Hom.:

AF XY:

0.00967

AC XY:

1305

AN XY:

134884

show subpopulations

Gnomad AFR exome

AF:

0.00198

Gnomad AMR exome

AF:

0.00636

Gnomad ASJ exome

AF:

0.0153

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00105

Gnomad FIN exome

AF:

0.0131

Gnomad NFE exome

AF:

0.0141

Gnomad OTH exome

AF:

0.0120

GnomAD4 exome

AF:

0.0122

AC:

17767

AN:

1459588

Hom.:

130

Cov.:

AF XY:

0.0121

AC XY:

8815

AN XY:

726040

show subpopulations

Gnomad4 AFR exome

AF:

0.00161

Gnomad4 AMR exome

AF:

0.00677

Gnomad4 ASJ exome

AF:

0.0156

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.000976

Gnomad4 FIN exome

AF:

0.0131

Gnomad4 NFE exome

AF:

0.0140

Gnomad4 OTH exome

AF:

0.0101

GnomAD4 genome

AF:

0.00895

AC:

1364

AN:

152342

Hom.:

Cov.:

AF XY:

0.00842

AC XY:

627

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.00197

Gnomad4 AMR

AF:

0.00666

Gnomad4 ASJ

AF:

0.0135

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.0106

Gnomad4 NFE

AF:

0.0146

Gnomad4 OTH

AF:

0.00851

Alfa

AF:

0.0133

Hom.:

Bravo

AF:

0.00852

TwinsUK

AF:

0.0108

AC:

ALSPAC

AF:

0.0163

AC:

ESP6500AA

AF:

0.00204

AC:

ESP6500EA

AF:

0.0129

AC:

111

ExAC

AF:

0.00946

AC:

1149

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.0140

EpiControl

AF:

0.0168

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jan 08, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.31

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.31

T;.

Eigen

Uncertain

0.23

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Uncertain

0.90

LIST_S2

Pathogenic

0.97

D;D

MetaRNN

Benign

0.012

T;T

MetaSVM

Benign

-0.67

MutationAssessor

Benign

-0.94

N;N

PrimateAI

Uncertain

0.75

PROVEAN

Pathogenic

-4.9

D;D

REVEL

Benign

0.17

Sift

Uncertain

0.0010

D;D

Sift4G

Pathogenic

0.0010

D;D

Polyphen

1.0

D;.

Vest4

0.80

MVP

0.80

MPC

0.63

ClinPred

0.062

GERP RS

3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

Varity_R

0.78

gMVP

0.74

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