6-36131273-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -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 (★).

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

Publications

18 publications found

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:

BRPF3-AS1 (HGNC:55591): (BRPF3 antisense RNA 1)

BRPF3-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 775077.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 14 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002754.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPK13	NM_002754.5	MANE Select	c.122C>T	p.Ser41Leu	missense splice_region	Exon 2 of 12	NP_002745.1	O15264-1
	MAPK13	NR_072996.2		n.192C>T		splice_region non_coding_transcript_exon	Exon 2 of 10

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MAPK13	ENST00000211287.9	TSL:1 MANE Select	c.122C>T	p.Ser41Leu	missense splice_region	Exon 2 of 12	ENSP00000211287.4	O15264-1
MAPK13	ENST00000373766.9	TSL:1	c.122C>T	p.Ser41Leu	missense splice_region	Exon 2 of 10	ENSP00000362871.5	O15264-2
MAPK13	ENST00000373759.1	TSL:5	c.-113C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 8	ENSP00000362864.1	Q5R3E6

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

GnomAD2 exomes

AF:

0.00953

AC:

2373

AN:

248876

AF XY:

0.00967

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 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

African (AFR)

AF:

0.00161

AC:

AN:

33454

American (AMR)

AF:

0.00677

AC:

302

AN:

44606

Ashkenazi Jewish (ASJ)

AF:

0.0156

AC:

406

AN:

26000

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39680

South Asian (SAS)

AF:

0.000976

AC:

AN:

86086

European-Finnish (FIN)

AF:

0.0131

AC:

693

AN:

52992

Middle Eastern (MID)

AF:

0.00799

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.0140

AC:

15572

AN:

1110710

Other (OTH)

AF:

0.0101

AC:

607

AN:

60302

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

936

1872

2809

3745

4681

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

574

1148

1722

2296

2870

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00895

AC:

1364

AN:

152342

Hom.:

Cov.:

AF XY:

0.00842

AC XY:

627

AN XY:

74494

show subpopulations

African (AFR)

AF:

0.00197

AC:

AN:

41582

American (AMR)

AF:

0.00666

AC:

102

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0135

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00124

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0106

AC:

113

AN:

10622

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0146

AC:

994

AN:

68030

Other (OTH)

AF:

0.00851

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

133

200

266

333

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0126

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

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.31

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.31

Eigen

Uncertain

0.23

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Uncertain

0.90

LIST_S2

Pathogenic

0.97

MetaRNN

Benign

0.012

MetaSVM

Benign

-0.67

MutationAssessor

Benign

-0.94

PhyloP100

4.9

PrimateAI

Uncertain

0.75

PROVEAN

Pathogenic

-4.9

REVEL

Benign

0.17

Sift

Uncertain

0.0010

Sift4G

Pathogenic

0.0010

Polyphen

1.0

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

Mutation Taster

=290/10

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over