10-48405106-G-GAT

Variant summary

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

The NM_001323329.2(MAPK8):c.252+146_252+147dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 232,544 control chromosomes in the GnomAD database, including 14,932 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.45 (14800 hom., cov: 0)
  • Exomes 𝑓: 0.26 (132 hom.)
• Consequence: MAPK8 NM_001323329.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.163

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 10-48405106-G-GAT is Benign according to our data. Variant chr10-48405106-G-GAT is described in ClinVar as [Benign]. Clinvar id is 1232348.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.807 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAPK8	NM_001323329.2	c.252+146_252+147dup		intron_variant		ENST00000374189.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAPK8	ENST00000374189.6	c.252+146_252+147dup		intron_variant		5	NM_001323329.2	A1

Frequencies

GnomAD3 genomes AF: 0.446 AC: 64344 AN: 144214 Hom.: 14814 Cov.: 0

Gnomad AFR AF: 0.308

Gnomad AMI AF: 0.513

Gnomad AMR AF: 0.429

Gnomad ASJ AF: 0.385

Gnomad EAS AF: 0.829

Gnomad SAS AF: 0.556

Gnomad FIN AF: 0.502

Gnomad MID AF: 0.463

Gnomad NFE AF: 0.492

Gnomad OTH AF: 0.458

GnomAD4 exome AF: 0.262 AC: 23117 AN: 88270 Hom.: 132 AF XY: 0.266 AC XY: 12595 AN XY: 47370

Gnomad4 AFR exome AF: 0.161

Gnomad4 AMR exome AF: 0.241

Gnomad4 ASJ exome AF: 0.216

Gnomad4 EAS exome AF: 0.419

Gnomad4 SAS exome AF: 0.101

Gnomad4 FIN exome AF: 0.264

Gnomad4 NFE exome AF: 0.263

Gnomad4 OTH exome AF: 0.247

GnomAD4 genome AF: 0.446 AC: 64343 AN: 144274 Hom.: 14800 Cov.: 0 AF XY: 0.451 AC XY: 31596 AN XY: 70100

Gnomad4 AFR AF: 0.307

Gnomad4 AMR AF: 0.429

Gnomad4 ASJ AF: 0.385

Gnomad4 EAS AF: 0.828

Gnomad4 SAS AF: 0.556

Gnomad4 FIN AF: 0.502

Gnomad4 NFE AF: 0.491

Gnomad4 OTH AF: 0.457

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: rs10657070; hg19: chr10-49613149;