rs150922772

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000373766.9(MAPK13):c.691T>G(p.Cys231Gly) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00234 in 1,610,656 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/19 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0025 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0023 ( 7 hom. )

Consequence

MAPK13
ENST00000373766.9 missense, splice_region

Scores

Splicing: ADA: 0.0002903

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -4.18

Publications

4 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=0.0040469766).

BP6

Variant 6-36138880-T-G is Benign according to our data. Variant chr6-36138880-T-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2656513.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000373766.9. 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.843T>G	p.Ala281Ala	splice_region synonymous	Exon 11 of 12	NP_002745.1	O15264-1
	MAPK13	NR_072996.2		n.761T>G		splice_region non_coding_transcript_exon	Exon 9 of 10

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MAPK13	ENST00000373766.9	TSL:1	c.691T>G	p.Cys231Gly	missense splice_region	Exon 9 of 10	ENSP00000362871.5	O15264-2
MAPK13	ENST00000211287.9	TSL:1 MANE Select	c.843T>G	p.Ala281Ala	splice_region synonymous	Exon 11 of 12	ENSP00000211287.4	O15264-1
MAPK13	ENST00000874020.1		c.1056T>G	p.Ala352Ala	splice_region synonymous	Exon 11 of 12	ENSP00000544079.1

Frequencies

GnomAD3 genomes

AF:

0.00250

AC:

381

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000313

Gnomad AMI

AF:

0.0230

Gnomad AMR

AF:

0.000916

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0137

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00268

Gnomad OTH

AF:

0.00191

GnomAD2 exomes

AF:

0.00237

AC:

586

AN:

247730

AF XY:

0.00235

show subpopulations

Gnomad AFR exome

AF:

0.000309

Gnomad AMR exome

AF:

0.000979

Gnomad ASJ exome

AF:

0.000103

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0118

Gnomad NFE exome

AF:

0.00246

Gnomad OTH exome

AF:

0.00166

GnomAD4 exome

AF:

0.00232

AC:

3388

AN:

1458324

Hom.:

Cov.:

AF XY:

0.00231

AC XY:

1673

AN XY:

725330

show subpopulations

African (AFR)

AF:

0.000391

AC:

AN:

33284

American (AMR)

AF:

0.000841

AC:

AN:

44020

Ashkenazi Jewish (ASJ)

AF:

0.000155

AC:

AN:

25864

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39662

South Asian (SAS)

AF:

0.000395

AC:

AN:

86004

European-Finnish (FIN)

AF:

0.00982

AC:

523

AN:

53250

Middle Eastern (MID)

AF:

0.00104

AC:

AN:

5746

European-Non Finnish (NFE)

AF:

0.00240

AC:

2662

AN:

1110314

Other (OTH)

AF:

0.00178

AC:

107

AN:

60180

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

173

345

518

690

863

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

184

276

368

460

<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:

0.00250

AC:

381

AN:

152332

Hom.:

Cov.:

AF XY:

0.00275

AC XY:

205

AN XY:

74484

show subpopulations

African (AFR)

AF:

0.000313

AC:

AN:

41590

American (AMR)

AF:

0.000915

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.000207

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0137

AC:

146

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00268

AC:

182

AN:

68024

Other (OTH)

AF:

0.00189

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00216

Hom.:

Bravo

AF:

0.00168

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00182

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00267

AC:

ExAC

AF:

0.00185

AC:

224

EpiCase

AF:

0.00234

EpiControl

AF:

0.00255

ClinVar

ClinVar submissions

Significance:Likely 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

0.050

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.24

CADD

Benign

0.40

(source)

DANN

Benign

0.43

Eigen

Benign

-0.79

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.039

LIST_S2

Benign

0.20

MetaRNN

Benign

0.0040

MetaSVM

Benign

-0.84

PhyloP100

-4.2

PROVEAN

Benign

-0.14

REVEL

Benign

0.057

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.041

Vest4

0.23

MVP

0.35

ClinPred

0.013

GERP RS

-9.4

Mutation Taster

=87/13

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00029

dbscSNV1_RF

Benign

0.040

SpliceAI score (max)

0.020

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