NM_001323329.2:c.871+66G>A

Variant names:

• chr10-48426136-G-A
• rs113214129
• NM_001323329.2:c.871+66G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001323329.2(MAPK8):​c.871+66G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0588 in 1,320,640 control chromosomes in the GnomAD database, including 4,010 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.061 (623 hom., cov: 32)
  • Exomes 𝑓: 0.058 (3387 hom.)
• Consequence: MAPK8 NM_001323329.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.220
• Publications: 4 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 10-48426136-G-A is Benign according to our data. Variant chr10-48426136-G-A is described in ClinVar as Benign. ClinVar VariationId is 2688159.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.207 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPK8	NM_001323329.2	MANE Select	c.871+66G>A		intron	N/A	NP_001310258.1	P45983-1
	MAPK8	NM_001278547.2		c.871+66G>A		intron	N/A	NP_001265476.1	A1L4K2
	MAPK8	NM_001323322.2		c.871+66G>A		intron	N/A	NP_001310251.1	P45983-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPK8	ENST00000374189.6	TSL:5 MANE Select	c.871+66G>A		intron	N/A	ENSP00000363304.1	P45983-1
	MAPK8	ENST00000374176.8	TSL:1	c.871+66G>A		intron	N/A	ENSP00000363291.4	P45983-4
	MAPK8	ENST00000374179.8	TSL:1	c.871+66G>A		intron	N/A	ENSP00000363294.3	P45983-3

Frequencies

GnomAD3 genomes AF: 0.0612 AC: 9287 AN: 151706 Hom.: 623 Cov.: 32

Gnomad AFR AF: 0.0275

Gnomad AMI AF: 0.0571

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.0657

Gnomad EAS AF: 0.0275

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.0417

Gnomad MID AF: 0.0353

Gnomad NFE AF: 0.0460

Gnomad OTH AF: 0.0637

GnomAD4 exome AF: 0.0585 AC: 68338 AN: 1168814 Hom.: 3387 Cov.: 15 AF XY: 0.0601 AC XY: 34973 AN XY: 581502

African (AFR) AF: 0.0258 AC: 679 AN: 26342

American (AMR) AF: 0.268 AC: 7657 AN: 28574

Ashkenazi Jewish (ASJ) AF: 0.0710 AC: 1365 AN: 19224

East Asian (EAS) AF: 0.0168 AC: 622 AN: 37068

South Asian (SAS) AF: 0.167 AC: 9638 AN: 57564

European-Finnish (FIN) AF: 0.0471 AC: 2017 AN: 42810

Middle Eastern (MID) AF: 0.0348 AC: 173 AN: 4966

European-Non Finnish (NFE) AF: 0.0477 AC: 43067 AN: 902706

Other (OTH) AF: 0.0630 AC: 3120 AN: 49560

GnomAD4 genome AF: 0.0613 AC: 9303 AN: 151826 Hom.: 623 Cov.: 32 AF XY: 0.0663 AC XY: 4919 AN XY: 74206

African (AFR) AF: 0.0275 AC: 1140 AN: 41428

American (AMR) AF: 0.213 AC: 3248 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.0657 AC: 228 AN: 3470

East Asian (EAS) AF: 0.0276 AC: 143 AN: 5188

South Asian (SAS) AF: 0.163 AC: 783 AN: 4810

European-Finnish (FIN) AF: 0.0417 AC: 437 AN: 10468

Middle Eastern (MID) AF: 0.0345 AC: 10 AN: 290

European-Non Finnish (NFE) AF: 0.0460 AC: 3122 AN: 67904

Other (OTH) AF: 0.0664 AC: 140 AN: 2110

Alfa AF: 0.0536 Hom.: 45

Bravo AF: 0.0686

Asia WGS AF: 0.120 AC: 415 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.9
DANN	Benign	0.67
PhyloP100		-0.22
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs113214129; hg19: chr10-49634179; COSMIC: COSV64410953; COSMIC: COSV64410953;