10-48425834-A-AATACATT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001323329.2(MAPK8):c.689-54_689-53insATACATT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.50 (19837 hom., cov: 0)
  • Exomes 𝑓: 0.52 (115502 hom.)
• Consequence: MAPK8 NM_001323329.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.380

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 -10 ACMG points.

• BP6: Variant 10-48425834-A-AATACATT is Benign according to our data. Variant chr10-48425834-A-AATACATT is described in ClinVar as [Benign]. Clinvar id is 1245652.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.62 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAPK8	NM_001323329.2	c.689-54_689-53insATACATT		intron_variant		ENST00000374189.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAPK8	ENST00000374189.6	c.689-54_689-53insATACATT		intron_variant		5	NM_001323329.2	A1

Frequencies

GnomAD3 genomes AF: 0.503 AC: 76388 AN: 151766 Hom.: 19837 Cov.: 0

Gnomad AFR AF: 0.374

Gnomad AMI AF: 0.562

Gnomad AMR AF: 0.488

Gnomad ASJ AF: 0.587

Gnomad EAS AF: 0.638

Gnomad SAS AF: 0.395

Gnomad FIN AF: 0.552

Gnomad MID AF: 0.713

Gnomad NFE AF: 0.569

Gnomad OTH AF: 0.539

GnomAD4 exome AF: 0.518 AC: 429259 AN: 828340 Hom.: 115502 Cov.: 11 AF XY: 0.516 AC XY: 217121 AN XY: 420564

Gnomad4 AFR exome AF: 0.340

Gnomad4 AMR exome AF: 0.479

Gnomad4 ASJ exome AF: 0.557

Gnomad4 EAS exome AF: 0.646

Gnomad4 SAS exome AF: 0.360

Gnomad4 FIN exome AF: 0.515

Gnomad4 NFE exome AF: 0.529

Gnomad4 OTH exome AF: 0.526

GnomAD4 genome AF: 0.503 AC: 76413 AN: 151884 Hom.: 19837 Cov.: 0 AF XY: 0.503 AC XY: 37307 AN XY: 74234

Gnomad4 AFR AF: 0.373

Gnomad4 AMR AF: 0.488

Gnomad4 ASJ AF: 0.587

Gnomad4 EAS AF: 0.638

Gnomad4 SAS AF: 0.397

Gnomad4 FIN AF: 0.552

Gnomad4 NFE AF: 0.569

Gnomad4 OTH AF: 0.533

Alfa AF: 0.520 Hom.: 573

Asia WGS AF: 0.484 AC: 1683 AN: 3478

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 13, 2021

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs771642181; hg19: chr10-49633877;