10-48427029-T-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate 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, single submitter B:1
• Conservation: PhyloP100: -0.461

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

Verdict is Benign. Variant got -14 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 id is 1289713.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0636 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAPK8	NM_001323329.2	c.997-51T>A		intron_variant		ENST00000374189.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAPK8	ENST00000374189.6	c.997-51T>A		intron_variant		5	NM_001323329.2	A1

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

GnomAD3 exomes AF: 0.0340 AC: 8380 AN: 246724 Hom.: 172 AF XY: 0.0333 AC XY: 4443 AN XY: 133312

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 SAS exome AF: 0.0174

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

Gnomad4 AFR exome AF: 0.0633

Gnomad4 AMR exome AF: 0.0258

Gnomad4 ASJ exome AF: 0.0415

Gnomad4 EAS exome AF: 0.0000785

Gnomad4 SAS exome AF: 0.0184

Gnomad4 FIN exome AF: 0.0349

Gnomad4 NFE exome AF: 0.0391

Gnomad4 OTH exome AF: 0.0383

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

Gnomad4 AFR AF: 0.0656

Gnomad4 AMR AF: 0.0355

Gnomad4 ASJ AF: 0.0360

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0151

Gnomad4 FIN AF: 0.0334

Gnomad4 NFE AF: 0.0398

Gnomad4 OTH AF: 0.0482

Alfa AF: 0.0240 Hom.: 18

Bravo AF: 0.0446

Asia WGS AF: 0.00867 AC: 30 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 22, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	0.56
Dann	Benign	0.80

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: rs3730160; hg19: chr10-49635072;