rs1031739

Variant names:

• chr4-86308524-G-A
• rs1031739
• NM_138982.4:c.-7+46006C>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.-7+46006C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.342 in 152,050 control chromosomes in the GnomAD database, including 9,039 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 0.34 (9039 hom., cov: 32)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: MAPK10 NM_138982.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0420
• Publications: 3 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 (NFE) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138982.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPK10	NM_138982.4	MANE Select	c.-7+46006C>T		intron	N/A	NP_620448.1
	MAPK10	NM_001318069.2		c.-7+46006C>T		intron	N/A	NP_001304998.1
	MAPK10	NM_001318067.1		c.-7+46006C>T		intron	N/A	NP_001304996.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPK10	ENST00000641462.2	MANE Select	c.-7+46006C>T		intron	N/A	ENSP00000493435.1
	MAPK10	ENST00000638225.1	TSL:1	c.-148+46006C>T		intron	N/A	ENSP00000491866.1
	MAPK10	ENST00000395160.9	TSL:1	c.-7+46006C>T		intron	N/A	ENSP00000378589.5

Frequencies

GnomAD3 genomes AF: 0.342 AC: 51918 AN: 151930 Hom.: 9029 Cov.: 32

Gnomad AFR AF: 0.278

Gnomad AMI AF: 0.458

Gnomad AMR AF: 0.363

Gnomad ASJ AF: 0.342

Gnomad EAS AF: 0.264

Gnomad SAS AF: 0.315

Gnomad FIN AF: 0.337

Gnomad MID AF: 0.341

Gnomad NFE AF: 0.383

Gnomad OTH AF: 0.320

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.342 AC: 51965 AN: 152048 Hom.: 9039 Cov.: 32 AF XY: 0.338 AC XY: 25137 AN XY: 74308

African (AFR) AF: 0.278 AC: 11524 AN: 41476

American (AMR) AF: 0.363 AC: 5550 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.342 AC: 1187 AN: 3468

East Asian (EAS) AF: 0.265 AC: 1369 AN: 5168

South Asian (SAS) AF: 0.314 AC: 1515 AN: 4820

European-Finnish (FIN) AF: 0.337 AC: 3561 AN: 10554

Middle Eastern (MID) AF: 0.346 AC: 101 AN: 292

European-Non Finnish (NFE) AF: 0.383 AC: 26064 AN: 67972

Other (OTH) AF: 0.320 AC: 676 AN: 2110

Alfa AF: 0.355 Hom.: 1590

Bravo AF: 0.340

Asia WGS AF: 0.256 AC: 889 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.8
DANN	Benign	0.54
PhyloP100		0.042
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: rs1031739; hg19: chr4-87229677;