Genetic Variant MAPK13:p.Val39Leu (chr6-36130697-G-C) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_002754.5(MAPK13):c.115G>C(p.Val39Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000154 in 1,294,930 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V39M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 28)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

MAPK13
NM_002754.5 missense

Scores

Clinical Significance

Not reported in ClinVar

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 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.907

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>C	p.Val39Leu	missense	Exon 1 of 12	NP_002745.1	O15264-1
	MAPK13	NR_072996.2		n.185G>C		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>C	p.Val39Leu	missense	Exon 1 of 12	ENSP00000211287.4	O15264-1
MAPK13	ENST00000373766.9	TSL:1	c.115G>C	p.Val39Leu	missense	Exon 1 of 10	ENSP00000362871.5	O15264-2
MAPK13	ENST00000373759.1	TSL:5	c.-120G>C		5_prime_UTR_premature_start_codon_gain	Exon 1 of 8	ENSP00000362864.1	Q5R3E6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000522

AC:

AN:

191468

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.0000117

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000154

AC:

AN:

1294930

Hom.:

Cov.:

AF XY:

0.00000154

AC XY:

AN XY:

648990

show subpopulations

African (AFR)

AF:

0.00

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:

0.00

AC:

AN:

80292

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50186

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4966

European-Non Finnish (NFE)

AF:

0.00000203

AC:

AN:

983908

Other (OTH)

AF:

0.00

AC:

AN:

53572

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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

Cov.:

ExAC

AF:

0.00000837

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.98

BayesDel_addAF

Pathogenic

0.20

BayesDel_noAF

Uncertain

0.050

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.38

Eigen

Uncertain

0.30

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.95

M_CAP

Pathogenic

0.64

MetaRNN

Pathogenic

0.91

MetaSVM

Uncertain

-0.25

MutationAssessor

Pathogenic

3.2

PhyloP100

9.7

PrimateAI

Pathogenic

0.84

PROVEAN

Uncertain

-2.7

REVEL

Uncertain

0.46

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.17

Vest4

0.76

MutPred

0.80

Loss of MoRF binding (P = 0.1232)

MVP

0.82

MPC

0.28

ClinPred

0.96

GERP RS

3.4

PromoterAI

-0.024

Neutral

(source)

Varity_R

0.96

gMVP

0.76

Mutation Taster

=59/41

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over