Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_138982.4(MAPK10):c.1271G>A(p.Ser424Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: not found (cov: 32)

Consequence

MAPK10
NM_138982.4 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 3.39

Publications

0 publications found

Variant links:

Genes affected

MAPK10 (HGNC:6872): (mitogen-activated protein kinase 10) The protein encoded by this gene is a member of the MAP kinase family. MAP kinases act as integration points for multiple biochemical signals, and thus are involved in a wide variety of cellular processes, such as proliferation, differentiation, transcription regulation and development. This kinase is specifically expressed in a subset of neurons in the nervous system, and is activated by threonine and tyrosine phosphorylation. Targeted deletion of this gene in mice suggests that it may have a role in stress-induced neuronal apoptosis. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. A recent study provided evidence for translational readthrough in this gene, and expression of an additional C-terminally extended isoform via the use of an alternative in-frame translation termination codon. [provided by RefSeq, Dec 2017]

MAPK10 Gene-Disease associations (from GenCC):

Lennox-Gastaut syndrome
Inheritance: AD Classification: LIMITED Submitted by: G2P

MAPK10 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15940046).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138982.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
MAPK10	NM_138982.4	MANE Select	c.1271G>A	p.Ser424Asn	missense	Exon 14 of 14	NP_620448.1
MAPK10	NM_001318069.2		c.1271G>A	p.Ser424Asn	missense	Exon 14 of 14	NP_001304998.1
MAPK10	NM_001318067.1		c.1271G>A	p.Ser424Asn	missense	Exon 13 of 13	NP_001304996.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
MAPK10	ENST00000641462.2	MANE Select	c.1271G>A	p.Ser424Asn	missense	Exon 14 of 14	ENSP00000493435.1
MAPK10	ENST00000638225.1	TSL:1	c.1157G>A	p.Ser386Asn	missense	Exon 14 of 14	ENSP00000491866.1
MAPK10	ENST00000310816.8	TSL:1	n.*780G>A		non_coding_transcript_exon	Exon 14 of 14	ENSP00000309857.4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

Prostate cancer (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.053

BayesDel_noAF

Benign

-0.31

CADD

Uncertain

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.37

Eigen

Benign

-0.11

Eigen_PC

Benign

0.15

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.015

MetaRNN

Benign

0.16

MetaSVM

Benign

-0.74

MutationAssessor

Benign

1.4

PhyloP100

3.4

PROVEAN

Benign

-0.17

REVEL

Uncertain

0.31

Sift

Benign

0.61

Sift4G

Benign

0.64

Polyphen

0.0020

Vest4

0.19

MutPred

0.18

Loss of phosphorylation at S424 (P = 0.0118)

MVP

0.53

ClinPred

0.63

GERP RS

5.7

Varity_R

0.22

gMVP

0.69

Mutation Taster

=54/46

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.

rs193921096

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over