4-86261283-T-C

Position:

• chr4-86261283-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_138982.4(MAPK10):​c.-6-66876A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 152,194 control chromosomes in the GnomAD database, including 2,993 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 0.18 (2993 hom., cov: 33)
• Consequence: MAPK10 NM_138982.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.433

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.287 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAPK10	NM_138982.4	c.-6-66876A>G		intron_variant		ENST00000641462.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAPK10	ENST00000641462.2	c.-6-66876A>G		intron_variant			NM_138982.4	P4

Frequencies

GnomAD3 genomes AF: 0.184 AC: 28041 AN: 152076 Hom.: 2979 Cov.: 33

Gnomad AFR AF: 0.291

Gnomad AMI AF: 0.0614

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.0733

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.201

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

GnomAD4 genome AF: 0.185 AC: 28091 AN: 152194 Hom.: 2993 Cov.: 33 AF XY: 0.182 AC XY: 13522 AN XY: 74416

Gnomad4 AFR AF: 0.291

Gnomad4 AMR AF: 0.155

Gnomad4 ASJ AF: 0.235

Gnomad4 EAS AF: 0.0731

Gnomad4 SAS AF: 0.109

Gnomad4 FIN AF: 0.102

Gnomad4 NFE AF: 0.151

Gnomad4 OTH AF: 0.201

Alfa AF: 0.139 Hom.: 816

Bravo AF: 0.193

Asia WGS AF: 0.110 AC: 387 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.2
DANN	Benign	0.55

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: rs9307016; hg19: chr4-87182436;