rs3775182

Variant names:

• chr4-86058430-G-T
• rs3775182
• NM_138982.4:c.1110+5836C>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.1110+5836C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0742 in 149,234 control chromosomes in the GnomAD database, including 968 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 0.074 (968 hom., cov: 30)
• Consequence: MAPK10 NM_138982.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05
• Publications: 12 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAPK10	NM_138982.4	c.1110+5836C>A		intron_variant	Intron 11 of 13	ENST00000641462.2	NP_620448.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAPK10	ENST00000641462.2	c.1110+5836C>A		intron_variant	Intron 11 of 13		NM_138982.4	ENSP00000493435.1

Frequencies

GnomAD3 genomes AF: 0.0742 AC: 11064 AN: 149120 Hom.: 966 Cov.: 30

Gnomad AFR AF: 0.0214

Gnomad AMI AF: 0.0622

Gnomad AMR AF: 0.0624

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.182

Gnomad SAS AF: 0.0893

Gnomad FIN AF: 0.0650

Gnomad MID AF: 0.115

Gnomad NFE AF: 0.0980

Gnomad OTH AF: 0.0775

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

GnomAD4 genome AF: 0.0742 AC: 11077 AN: 149234 Hom.: 968 Cov.: 30 AF XY: 0.0740 AC XY: 5392 AN XY: 72850

African (AFR) AF: 0.0214 AC: 850 AN: 39740

American (AMR) AF: 0.0623 AC: 940 AN: 15086

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 380 AN: 3432

East Asian (EAS) AF: 0.182 AC: 935 AN: 5134

South Asian (SAS) AF: 0.0896 AC: 430 AN: 4798

European-Finnish (FIN) AF: 0.0650 AC: 678 AN: 10430

Middle Eastern (MID) AF: 0.110 AC: 32 AN: 292

European-Non Finnish (NFE) AF: 0.0980 AC: 6603 AN: 67348

Other (OTH) AF: 0.0834 AC: 173 AN: 2074

Alfa AF: 0.0909 Hom.: 1589

Bravo AF: 0.0720

Asia WGS AF: 0.114 AC: 396 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.35
DANN	Benign	0.28
PhyloP100		-1.0
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: rs3775182; hg19: chr4-86979583;