NM_001323329.2:c.252+1367G>A

Variant names:

• chr10-48406348-G-A
• rs3827680
• NM_001323329.2:c.252+1367G>A

Variant summary

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

The NM_001323329.2(MAPK8):​c.252+1367G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.46 in 152,010 control chromosomes in the GnomAD database, including 16,293 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 0.46 (16293 hom., cov: 32)
• Consequence: MAPK8 NM_001323329.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.519
• Publications: 3 publications found

Genes affected

MAPK8 (HGNC:6881): (mitogen-activated protein kinase 8) The protein encoded by this gene is a member of the MAP kinase family. MAP kinases act as an integration point for multiple biochemical signals, and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation and development. This kinase is activated by various cell stimuli, and targets specific transcription factors, and thus mediates immediate-early gene expression in response to cell stimuli. The activation of this kinase by tumor-necrosis factor alpha (TNF-alpha) is found to be required for TNF-alpha induced apoptosis. This kinase is also involved in UV radiation induced apoptosis, which is thought to be related to cytochrom c-mediated cell death pathway. Studies of the mouse counterpart of this gene suggested that this kinase play a key role in T cell proliferation, apoptosis and differentiation. Several alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Apr 2016]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.556 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001323329.2. 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
	MAPK8	NM_001323329.2	MANE Select	c.252+1367G>A		intron	N/A	NP_001310258.1
	MAPK8	NM_001278547.2		c.252+1367G>A		intron	N/A	NP_001265476.1
	MAPK8	NM_001323322.2		c.252+1367G>A		intron	N/A	NP_001310251.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPK8	ENST00000374189.6	TSL:5 MANE Select	c.252+1367G>A		intron	N/A	ENSP00000363304.1
	MAPK8	ENST00000374176.8	TSL:1	c.252+1367G>A		intron	N/A	ENSP00000363291.4
	MAPK8	ENST00000374179.8	TSL:1	c.252+1367G>A		intron	N/A	ENSP00000363294.3

Frequencies

GnomAD3 genomes AF: 0.460 AC: 69824 AN: 151892 Hom.: 16270 Cov.: 32

Gnomad AFR AF: 0.515

Gnomad AMI AF: 0.433

Gnomad AMR AF: 0.498

Gnomad ASJ AF: 0.366

Gnomad EAS AF: 0.362

Gnomad SAS AF: 0.575

Gnomad FIN AF: 0.447

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.426

Gnomad OTH AF: 0.427

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

GnomAD4 genome AF: 0.460 AC: 69901 AN: 152010 Hom.: 16293 Cov.: 32 AF XY: 0.463 AC XY: 34368 AN XY: 74296

African (AFR) AF: 0.515 AC: 21359 AN: 41452

American (AMR) AF: 0.498 AC: 7604 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.366 AC: 1270 AN: 3470

East Asian (EAS) AF: 0.361 AC: 1864 AN: 5160

South Asian (SAS) AF: 0.573 AC: 2759 AN: 4812

European-Finnish (FIN) AF: 0.447 AC: 4727 AN: 10580

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.426 AC: 28927 AN: 67952

Other (OTH) AF: 0.434 AC: 918 AN: 2116

Alfa AF: 0.441 Hom.: 5095

Bravo AF: 0.459

Asia WGS AF: 0.498 AC: 1732 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.0
DANN	Benign	0.46
PhyloP100		-0.52
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: rs3827680; hg19: chr10-49614391;