rs6815306

Variant names:

• chr4-86045174-C-A
• rs6815306
• NM_138982.4:c.1111-13743G>T

Variant summary

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

The NM_138982.4(MAPK10):​c.1111-13743G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.367 in 151,592 control chromosomes in the GnomAD database, including 12,171 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 0.37 (12171 hom., cov: 31)
• Consequence: MAPK10 NM_138982.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00100
• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.565 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAPK10	NM_138982.4	c.1111-13743G>T		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.1111-13743G>T		intron_variant	Intron 11 of 13		NM_138982.4	ENSP00000493435.1

Frequencies

GnomAD3 genomes AF: 0.367 AC: 55573 AN: 151474 Hom.: 12174 Cov.: 31

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.422

Gnomad AMR AF: 0.442

Gnomad ASJ AF: 0.421

Gnomad EAS AF: 0.504

Gnomad SAS AF: 0.583

Gnomad FIN AF: 0.608

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.430

Gnomad OTH AF: 0.403

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

GnomAD4 genome AF: 0.367 AC: 55578 AN: 151592 Hom.: 12171 Cov.: 31 AF XY: 0.381 AC XY: 28231 AN XY: 74084

African (AFR) AF: 0.122 AC: 5047 AN: 41328

American (AMR) AF: 0.442 AC: 6715 AN: 15196

Ashkenazi Jewish (ASJ) AF: 0.421 AC: 1460 AN: 3464

East Asian (EAS) AF: 0.505 AC: 2586 AN: 5124

South Asian (SAS) AF: 0.583 AC: 2804 AN: 4810

European-Finnish (FIN) AF: 0.608 AC: 6406 AN: 10536

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.430 AC: 29183 AN: 67834

Other (OTH) AF: 0.401 AC: 840 AN: 2094

Alfa AF: 0.418 Hom.: 22372

Bravo AF: 0.343

Asia WGS AF: 0.530 AC: 1838 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.8
DANN	Benign	0.45
PhyloP100		-0.0010
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: rs6815306; hg19: chr4-86966327;