Variant 6-36131368-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_002754.5(MAPK13):c.217C>G(p.Leu73Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,613,208 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 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

MAPK13
NM_002754.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.18

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 Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.75

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAPK13	NM_002754.5 link	c.217C>G	p.Leu73Val	missense_variant	2/12	ENST00000211287.9	NP_002745.1	O15264-1A0A024RD04
MAPK13	NR_072996.2 link	n.287C>G		non_coding_transcript_exon_variant	2/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAPK13	ENST00000211287.9 link	c.217C>G	p.Leu73Val	missense_variant	2/12	1	NM_002754.5	ENSP00000211287.4		O15264-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

250882

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135708

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1461032

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

726874

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152176

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000385

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000478

Bravo

AF:

0.0000189

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 05, 2022

The c.217C>G (p.L73V) alteration is located in exon 2 (coding exon 2) of the MAPK13 gene. This alteration results from a C to G substitution at nucleotide position 217, causing the leucine (L) at amino acid position 73 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.36

BayesDel_addAF

Benign

-0.0037

BayesDel_noAF

Uncertain

-0.070

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.30

T;.

Eigen

Uncertain

0.28

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Uncertain

0.89

LIST_S2

Pathogenic

0.98

D;D

M_CAP

Benign

0.030

MetaRNN

Pathogenic

0.75

D;D

MetaSVM

Benign

-0.55

MutationAssessor

Benign

-0.77

N;N

PrimateAI

Uncertain

0.65

PROVEAN

Uncertain

-2.6

D;D

REVEL

Uncertain

0.40

Sift

Uncertain

0.0010

D;D

Sift4G

Uncertain

0.029

D;D

Polyphen

1.0

D;.

Vest4

0.72

MutPred

0.64

Gain of methylation at K77 (P = 0.0797);Gain of methylation at K77 (P = 0.0797);

MVP

0.83

MPC

0.74

ClinPred

0.91

GERP RS

3.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.81

gMVP

0.55

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