6-36130659-T-C

Position:

chr6-36130659-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002754.5(MAPK13):c.77T>C(p.Val26Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000132 in 1,572,730 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000069 ( 0 hom., cov: 28)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

MAPK13
NM_002754.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.26

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:

MAPK13 (HGNC:):

MAPK13 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.087721586).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAPK13	NM_002754.5 linkuse as main transcript	c.77T>C	p.Val26Ala	missense_variant	1/12	ENST00000211287.9	NP_002745.1	O15264-1A0A024RD04
MAPK13	NR_072996.2 linkuse as main transcript	n.147T>C		non_coding_transcript_exon_variant	1/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MAPK13	ENST00000211287.9 linkuse as main transcript	c.77T>C	p.Val26Ala	missense_variant	1/12	1	NM_002754.5	ENSP00000211287.4	O15264-1
MAPK13	ENST00000373766.9 linkuse as main transcript	c.77T>C	p.Val26Ala	missense_variant	1/10	1		ENSP00000362871.5	O15264-2
MAPK13	ENST00000476951.5 linkuse as main transcript	n.188T>C		non_coding_transcript_exon_variant	2/5	3
MAPK13	ENST00000373759.1 linkuse as main transcript	c.-158T>C		upstream_gene_variant		5		ENSP00000362864.1	Q5R3E6

Frequencies

GnomAD3 genomes

AF:

0.0000695

AC:

AN:

143908

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000151

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000282

AC:

AN:

212936

Hom.:

AF XY:

0.0000338

AC XY:

AN XY:

118366

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000625

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000139

AC:

198

AN:

1428822

Hom.:

Cov.:

AF XY:

0.000128

AC XY:

AN XY:

711198

show subpopulations

Gnomad4 AFR exome

AF:

0.0000337

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000176

Gnomad4 OTH exome

AF:

0.0000681

GnomAD4 genome

AF:

0.0000695

AC:

AN:

143908

Hom.:

Cov.:

AF XY:

0.0000573

AC XY:

AN XY:

69822

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000151

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000116

Hom.:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000249

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

Nov 26, 2024

The c.77T>C (p.V26A) alteration is located in exon 1 (coding exon 1) of the MAPK13 gene. This alteration results from a T to C substitution at nucleotide position 77, causing the valine (V) at amino acid position 26 to be replaced by an alanine (A). 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

Benign

0.14

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.72

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.088

T;.

Eigen

Benign

-0.91

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.040

LIST_S2

Benign

0.43

T;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.088

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.87

L;L

PrimateAI

Uncertain

0.54

PROVEAN

Benign

0.30

N;N

REVEL

Benign

0.040

Sift

Benign

0.19

T;T

Sift4G

Benign

0.76

T;T

Polyphen

0.0

B;.

Vest4

0.055

MVP

0.32

MPC

0.22

ClinPred

0.015

GERP RS

0.080

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.37

gMVP

0.25

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