MAPK10 p.Val113Val

Variant names:

• chr4-86107249-G-G
• NM_138982.4:c.

Your query was ambiguous. Multiple possible variants found:

• chr4-86107250--
• chr4-86107250-G-A
• chr4-86107250-G-T
• chr4-86107250-G-C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_138982.4(MAPK10):​c. variant causes a exon region change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MAPK10 NM_138982.4 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.70
• Publications: 0 publications found

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPK10	NM_138982.4	MANE Select	c.		exon_region	Exon 5 of 14	NP_620448.1	P53779-1
	MAPK10	NM_001318069.2		c.		exon_region	Exon 5 of 14	NP_001304998.1	F8W9R5
	MAPK10	NM_001318067.1		c.		exon_region	Exon 4 of 13	NP_001304996.1	A0A286YF97

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPK10	ENST00000641462.2	MANE Select	c.		exon_region	Exon 5 of 14	ENSP00000493435.1	P53779-1
	MAPK10	ENST00000638225.1	TSL:1	c.		exon_region	Exon 5 of 14	ENSP00000491866.1	P53779-3
	MAPK10	ENST00000395160.9	TSL:1	c.		exon_region	Exon 5 of 14	ENSP00000378589.5	A0A1P0B7D2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.7

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr4-87028402;