Genetic Variant MAPK13:p.Val39Met (chr6-36130697-G-A) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_002754.5(MAPK13):c.115G>A(p.Val39Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000764 in 1,440,004 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000041 ( 0 hom., cov: 28)

Exomes 𝑓: 0.0000039 ( 0 hom. )

Consequence

MAPK13
NM_002754.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.71

Publications

1 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.817

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.115G>A	p.Val39Met	missense	Exon 1 of 12	NP_002745.1	O15264-1
	MAPK13	NR_072996.2		n.185G>A		non_coding_transcript_exon	Exon 1 of 10

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MAPK13	ENST00000211287.9	TSL:1 MANE Select	c.115G>A	p.Val39Met	missense	Exon 1 of 12	ENSP00000211287.4	O15264-1
MAPK13	ENST00000373766.9	TSL:1	c.115G>A	p.Val39Met	missense	Exon 1 of 10	ENSP00000362871.5	O15264-2
MAPK13	ENST00000373759.1	TSL:5	c.-120G>A		5_prime_UTR_premature_start_codon_gain	Exon 1 of 8	ENSP00000362864.1	Q5R3E6

Frequencies

GnomAD3 genomes

AF:

0.0000414

AC:

AN:

145086

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000153

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000209

AC:

AN:

191468

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.000451

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

0.00000386

AC:

AN:

1294918

Hom.:

Cov.:

AF XY:

0.00000308

AC XY:

AN XY:

648986

show subpopulations

African (AFR)

AF:

0.000113

AC:

AN:

26470

American (AMR)

AF:

0.00

AC:

AN:

40182

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23618

East Asian (EAS)

AF:

0.00

AC:

AN:

31736

South Asian (SAS)

AF:

0.0000125

AC:

AN:

80292

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50186

Middle Eastern (MID)

AF:

0.000201

AC:

AN:

4966

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

983896

Other (OTH)

AF:

0.00

AC:

AN:

53572

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000414

AC:

AN:

145086

Hom.:

Cov.:

AF XY:

0.0000708

AC XY:

AN XY:

70592

show subpopulations

African (AFR)

AF:

0.000153

AC:

AN:

39102

American (AMR)

AF:

0.00

AC:

AN:

14742

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3408

East Asian (EAS)

AF:

0.00

AC:

AN:

4246

South Asian (SAS)

AF:

0.00

AC:

AN:

4446

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9748

Middle Eastern (MID)

AF:

0.00

AC:

AN:

308

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

66192

Other (OTH)

AF:

0.00

AC:

AN:

2012

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

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:

0.000688

Hom.:

Bravo

AF:

0.0000264

ESP6500AA

AF:

0.000457

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000167

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.99

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Pathogenic

0.23

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.49

Eigen

Pathogenic

0.77

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.95

M_CAP

Pathogenic

0.53

MetaRNN

Pathogenic

0.82

MetaSVM

Uncertain

0.34

MutationAssessor

Pathogenic

3.7

PhyloP100

9.7

PrimateAI

Pathogenic

0.86

PROVEAN

Uncertain

-2.7

REVEL

Uncertain

0.59

Sift

Uncertain

0.0020

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.70

MVP

0.85

MPC

0.70

ClinPred

0.82

GERP RS

3.4

PromoterAI

-0.14

Neutral

(source)

Varity_R

0.92

gMVP

0.80

Mutation Taster

=55/45

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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