10-48427029-T-A

Variant names:

• chr10-48427029-T-A
• rs3730160
• NM_001323329.2:c.997-51T>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001323329.2(MAPK8):​c.997-51T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0374 in 1,367,280 control chromosomes in the GnomAD database, including 1,096 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.044 (167 hom., cov: 32)
  • Exomes 𝑓: 0.037 (929 hom.)
• Consequence: MAPK8 NM_001323329.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.461
• Publications: 5 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 10-48427029-T-A is Benign according to our data. Variant chr10-48427029-T-A is described in ClinVar as Benign. ClinVar VariationId is 1289713.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0636 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.997-51T>A		intron	N/A	NP_001310258.1	P45983-1
	MAPK8	NM_001278547.2		c.997-51T>A		intron	N/A	NP_001265476.1	A1L4K2
	MAPK8	NM_001323322.2		c.997-51T>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.997-51T>A		intron	N/A	ENSP00000363304.1	P45983-1
	MAPK8	ENST00000374176.8	TSL:1	c.997-51T>A		intron	N/A	ENSP00000363291.4	P45983-4
	MAPK8	ENST00000374179.8	TSL:1	c.997-51T>A		intron	N/A	ENSP00000363294.3	P45983-3

Frequencies

GnomAD3 genomes AF: 0.0437 AC: 6655 AN: 152166 Hom.: 168 Cov.: 32

Gnomad AFR AF: 0.0656

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.0355

Gnomad ASJ AF: 0.0360

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0151

Gnomad FIN AF: 0.0334

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0398

Gnomad OTH AF: 0.0487

GnomAD2 exomes AF: 0.0340 AC: 8380 AN: 246724 AF XY: 0.0333

Gnomad AFR exome AF: 0.0625

Gnomad AMR exome AF: 0.0246

Gnomad ASJ exome AF: 0.0404

Gnomad EAS exome AF: 0.0000551

Gnomad FIN exome AF: 0.0341

Gnomad NFE exome AF: 0.0418

Gnomad OTH exome AF: 0.0396

GnomAD4 exome AF: 0.0366 AC: 44488 AN: 1214996 Hom.: 929 Cov.: 16 AF XY: 0.0362 AC XY: 22371 AN XY: 617270

African (AFR) AF: 0.0633 AC: 1818 AN: 28722

American (AMR) AF: 0.0258 AC: 1138 AN: 44108

Ashkenazi Jewish (ASJ) AF: 0.0415 AC: 1014 AN: 24442

East Asian (EAS) AF: 0.0000785 AC: 3 AN: 38230

South Asian (SAS) AF: 0.0184 AC: 1484 AN: 80518

European-Finnish (FIN) AF: 0.0349 AC: 1824 AN: 52326

Middle Eastern (MID) AF: 0.0811 AC: 427 AN: 5268

European-Non Finnish (NFE) AF: 0.0391 AC: 34784 AN: 889318

Other (OTH) AF: 0.0383 AC: 1996 AN: 52064

GnomAD4 genome AF: 0.0437 AC: 6660 AN: 152284 Hom.: 167 Cov.: 32 AF XY: 0.0418 AC XY: 3110 AN XY: 74462

African (AFR) AF: 0.0656 AC: 2726 AN: 41544

American (AMR) AF: 0.0355 AC: 543 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0360 AC: 125 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5188

South Asian (SAS) AF: 0.0151 AC: 73 AN: 4832

European-Finnish (FIN) AF: 0.0334 AC: 354 AN: 10612

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0398 AC: 2704 AN: 68016

Other (OTH) AF: 0.0482 AC: 102 AN: 2116

Alfa AF: 0.0240 Hom.: 18

Bravo AF: 0.0446

Asia WGS AF: 0.00867 AC: 30 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.56
DANN	Benign	0.80
PhyloP100		-0.46
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: rs3730160; hg19: chr10-49635072;