4-86311831-A-G

Variant names:

• chr4-86311831-A-G
• rs11726269
• NM_138982.4:c.-7+42699T>C

Variant summary

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

The NM_138982.4(MAPK10):​c.-7+42699T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0686 in 152,174 control chromosomes in the GnomAD database, including 463 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 0.069 (463 hom., cov: 32)
• Consequence: MAPK10 NM_138982.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.274
• Publications: 5 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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAPK10	NM_138982.4	c.-7+42699T>C		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.-7+42699T>C		intron_variant	Intron 2 of 13		NM_138982.4	ENSP00000493435.1

Frequencies

GnomAD3 genomes AF: 0.0686 AC: 10436 AN: 152056 Hom.: 463 Cov.: 32

Gnomad AFR AF: 0.0176

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.0701

Gnomad ASJ AF: 0.0675

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0332

Gnomad FIN AF: 0.0945

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.0875

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

GnomAD4 genome AF: 0.0686 AC: 10433 AN: 152174 Hom.: 463 Cov.: 32 AF XY: 0.0664 AC XY: 4942 AN XY: 74398

African (AFR) AF: 0.0175 AC: 729 AN: 41562

American (AMR) AF: 0.0699 AC: 1067 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.0675 AC: 234 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5176

South Asian (SAS) AF: 0.0330 AC: 159 AN: 4818

European-Finnish (FIN) AF: 0.0945 AC: 1001 AN: 10588

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.101 AC: 6890 AN: 67988

Other (OTH) AF: 0.0870 AC: 184 AN: 2114

Alfa AF: 0.0795 Hom.: 334

Bravo AF: 0.0653

Asia WGS AF: 0.0170 AC: 60 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	5.3
DANN	Benign	0.57
PhyloP100		-0.27
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: rs11726269; hg19: chr4-87232984;