rs958

Variant names:

• chr4-86016721-C-T
• rs958
• NM_138982.4:c.*507G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_138982.4(MAPK10):​c.*507G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 157,020 control chromosomes in the GnomAD database, including 3,289 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 0.20 (3179 hom., cov: 32)
  • Exomes 𝑓: 0.18 (110 hom.)
• Consequence: MAPK10 NM_138982.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.861
• Publications: 17 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.244 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPK10	NM_138982.4	MANE Select	c.*507G>A		3_prime_UTR	Exon 14 of 14	NP_620448.1	P53779-1
	MAPK10	NM_001318069.2		c.*465G>A		3_prime_UTR	Exon 14 of 14	NP_001304998.1	F8W9R5
	MAPK10	NM_001318067.1		c.*507G>A		3_prime_UTR	Exon 13 of 13	NP_001304996.1	A0A286YF97

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPK10	ENST00000641462.2	MANE Select	c.*507G>A		3_prime_UTR	Exon 14 of 14	ENSP00000493435.1	P53779-1
	MAPK10	ENST00000638225.1	TSL:1	c.*507G>A		3_prime_UTR	Exon 14 of 14	ENSP00000491866.1	P53779-3
	MAPK10	ENST00000395160.9	TSL:1	c.*638G>A		3_prime_UTR	Exon 14 of 14	ENSP00000378589.5	A0A1P0B7D2

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30322 AN: 151912 Hom.: 3175 Cov.: 32

Gnomad AFR AF: 0.197

Gnomad AMI AF: 0.159

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.255

Gnomad SAS AF: 0.246

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.204

Gnomad OTH AF: 0.212

GnomAD4 exome AF: 0.181 AC: 904 AN: 4990 Hom.: 110 Cov.: 0 AF XY: 0.179 AC XY: 480 AN XY: 2680

African (AFR) AF: 0.167 AC: 7 AN: 42

American (AMR) AF: 0.129 AC: 154 AN: 1194

Ashkenazi Jewish (ASJ) AF: 0.179 AC: 5 AN: 28

East Asian (EAS) AF: 0.213 AC: 26 AN: 122

South Asian (SAS) AF: 0.204 AC: 85 AN: 416

European-Finnish (FIN) AF: 0.152 AC: 21 AN: 138

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4

European-Non Finnish (NFE) AF: 0.196 AC: 563 AN: 2872

Other (OTH) AF: 0.247 AC: 43 AN: 174

GnomAD4 genome AF: 0.200 AC: 30346 AN: 152030 Hom.: 3179 Cov.: 32 AF XY: 0.199 AC XY: 14768 AN XY: 74338

African (AFR) AF: 0.197 AC: 8149 AN: 41428

American (AMR) AF: 0.201 AC: 3071 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.221 AC: 766 AN: 3468

East Asian (EAS) AF: 0.256 AC: 1322 AN: 5170

South Asian (SAS) AF: 0.245 AC: 1181 AN: 4812

European-Finnish (FIN) AF: 0.127 AC: 1342 AN: 10576

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.204 AC: 13855 AN: 67960

Other (OTH) AF: 0.217 AC: 459 AN: 2112

Alfa AF: 0.201 Hom.: 4188

Bravo AF: 0.200

Asia WGS AF: 0.247 AC: 860 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	17
DANN	Benign	0.76
PhyloP100		0.86
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: rs958; hg19: chr4-86937874;