4-86250125-G-C

Variant names:

• chr4-86250125-G-C
• rs10516771
• NM_138982.4:c.-6-55718C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_138982.4(MAPK10):​c.-6-55718C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0634 in 152,212 control chromosomes in the GnomAD database, including 501 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.063 (501 hom., cov: 32)
• Consequence: MAPK10 NM_138982.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.340
• Publications: 2 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.129 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAPK10	NM_138982.4	c.-6-55718C>G		intron_variant	Intron 2 of 13	ENST00000641462.2	NP_620448.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAPK10	ENST00000641462.2	c.-6-55718C>G		intron_variant	Intron 2 of 13		NM_138982.4	ENSP00000493435.1

Frequencies

GnomAD3 genomes AF: 0.0633 AC: 9622 AN: 152092 Hom.: 497 Cov.: 32

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0403

Gnomad ASJ AF: 0.0444

Gnomad EAS AF: 0.00289

Gnomad SAS AF: 0.0423

Gnomad FIN AF: 0.0435

Gnomad MID AF: 0.0318

Gnomad NFE AF: 0.0383

Gnomad OTH AF: 0.0454

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0634 AC: 9649 AN: 152212 Hom.: 501 Cov.: 32 AF XY: 0.0617 AC XY: 4592 AN XY: 74418

African (AFR) AF: 0.132 AC: 5487 AN: 41516

American (AMR) AF: 0.0401 AC: 614 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0444 AC: 154 AN: 3470

East Asian (EAS) AF: 0.00289 AC: 15 AN: 5182

South Asian (SAS) AF: 0.0419 AC: 202 AN: 4824

European-Finnish (FIN) AF: 0.0435 AC: 461 AN: 10598

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0383 AC: 2606 AN: 68006

Other (OTH) AF: 0.0449 AC: 95 AN: 2114

Alfa AF: 0.0269 Hom.: 15

Bravo AF: 0.0658

Asia WGS AF: 0.0210 AC: 71 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.3
DANN	Benign	0.52
PhyloP100		0.34
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10516771; hg19: chr4-87171278;