rs958

chr4-86016721-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAPK10	NM_138982.4	c.*507G>A		3_prime_UTR_variant	14/14	ENST00000641462.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAPK10	ENST00000641462.2	c.*507G>A		3_prime_UTR_variant	14/14		NM_138982.4	P4

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

Gnomad4 AFR exome AF: 0.167

Gnomad4 AMR exome AF: 0.129

Gnomad4 ASJ exome AF: 0.179

Gnomad4 EAS exome AF: 0.213

Gnomad4 SAS exome AF: 0.204

Gnomad4 FIN exome AF: 0.152

Gnomad4 NFE exome AF: 0.196

Gnomad4 OTH exome AF: 0.247

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

Gnomad4 AFR AF: 0.197

Gnomad4 AMR AF: 0.201

Gnomad4 ASJ AF: 0.221

Gnomad4 EAS AF: 0.256

Gnomad4 SAS AF: 0.245

Gnomad4 FIN AF: 0.127

Gnomad4 NFE AF: 0.204

Gnomad4 OTH AF: 0.217

Alfa AF: 0.200 Hom.: 3208

Bravo AF: 0.200

Asia WGS AF: 0.247 AC: 860 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
Cadd	Benign	17
Dann	Benign	0.76

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

Publications

LitVar

Other links and lift over

dbSNP: rs958; hg19: chr4-86937874;