4-86068874-C-T

Variant names:

• chr4-86068874-C-T
• rs1469869
• NM_138982.4:c.803-919G>A

Variant summary

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

The NM_138982.4(MAPK10):​c.803-919G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.44 in 151,926 control chromosomes in the GnomAD database, including 15,338 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 0.44 (15338 hom., cov: 32)
• Consequence: MAPK10 NM_138982.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.91
• Publications: 8 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.549 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAPK10	NM_138982.4	c.803-919G>A		intron_variant	Intron 9 of 13	ENST00000641462.2	NP_620448.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAPK10	ENST00000641462.2	c.803-919G>A		intron_variant	Intron 9 of 13		NM_138982.4	ENSP00000493435.1

Frequencies

GnomAD3 genomes AF: 0.440 AC: 66748 AN: 151808 Hom.: 15332 Cov.: 32

Gnomad AFR AF: 0.556

Gnomad AMI AF: 0.421

Gnomad AMR AF: 0.340

Gnomad ASJ AF: 0.366

Gnomad EAS AF: 0.250

Gnomad SAS AF: 0.325

Gnomad FIN AF: 0.325

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.438

Gnomad OTH AF: 0.396

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

GnomAD4 genome AF: 0.440 AC: 66797 AN: 151926 Hom.: 15338 Cov.: 32 AF XY: 0.431 AC XY: 31998 AN XY: 74250

African (AFR) AF: 0.555 AC: 22989 AN: 41412

American (AMR) AF: 0.340 AC: 5189 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.366 AC: 1269 AN: 3466

East Asian (EAS) AF: 0.251 AC: 1299 AN: 5174

South Asian (SAS) AF: 0.325 AC: 1566 AN: 4824

European-Finnish (FIN) AF: 0.325 AC: 3436 AN: 10562

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.438 AC: 29721 AN: 67894

Other (OTH) AF: 0.399 AC: 841 AN: 2108

Alfa AF: 0.429 Hom.: 43777

Bravo AF: 0.443

Asia WGS AF: 0.296 AC: 1031 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.18
DANN	Benign	0.82
PhyloP100		-1.9
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: rs1469869; hg19: chr4-86990027;