rs193921096
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_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. 13/20 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
NM_138982.4 missense
Scores
2
10
Clinical Significance
Conservation
PhyloP100: 3.39
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP2
?
Missense variant where missense usually causes diseases, MAPK10
BP4
?
Computational evidence support a benign effect (MetaRNN=0.15940046).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MAPK10 | NM_138982.4 | c.1271G>A | p.Ser424Asn | missense_variant | 14/14 | ENST00000641462.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MAPK10 | ENST00000641462.2 | c.1271G>A | p.Ser424Asn | missense_variant | 14/14 | NM_138982.4 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Malignant tumor of prostate Uncertain:1
Uncertain significance, no assertion criteria provided | literature only | Science for Life laboratory, Karolinska Institutet | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;.;D;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;D;D;.;D;.;D;.;.;.;D;D;.;.;D;.;D;.;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D;D;D
Polyphen
0.0020, 0.0030, 0.0010
.;.;.;B;.;B;B;B;B;B;B;B;B;.;B;.;B;B;B;B;B;.;B;B;B;B;B;B;B;.;B;.;B;.;B;B;B;.;.;B;B;.;B;B;B;B
Vest4
0.19, 0.24
MutPred
Loss of phosphorylation at S424 (P = 0.0118);.;Loss of phosphorylation at S424 (P = 0.0118);.;.;.;Loss of phosphorylation at S424 (P = 0.0118);Loss of phosphorylation at S424 (P = 0.0118);Loss of phosphorylation at S424 (P = 0.0118);Loss of phosphorylation at S424 (P = 0.0118);Loss of phosphorylation at S424 (P = 0.0118);Loss of phosphorylation at S424 (P = 0.0118);Loss of phosphorylation at S424 (P = 0.0118);Loss of phosphorylation at S424 (P = 0.0118);Loss of phosphorylation at S424 (P = 0.0118);Loss of phosphorylation at S424 (P = 0.0118);.;.;.;.;.;.;Loss of phosphorylation at S424 (P = 0.0118);.;.;.;.;.;.;.;Loss of phosphorylation at S424 (P = 0.0118);.;Loss of phosphorylation at S424 (P = 0.0118);.;.;.;.;Loss of phosphorylation at S424 (P = 0.0118);.;Loss of phosphorylation at S424 (P = 0.0118);.;.;.;.;Loss of phosphorylation at S424 (P = 0.0118);Loss of phosphorylation at S424 (P = 0.0118);
MVP
0.53
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at