chr10-48405121-A-ATG

Position:

• chr10-48405121-A-ATG

Variant summary

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

The NM_001323329.2(MAPK8):​c.252+141_252+142insGT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 270,100 control chromosomes in the GnomAD database, including 1,781 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.090 (693 hom., cov: 29)
  • Exomes 𝑓: 0.13 (1088 hom.)
• Consequence: MAPK8 NM_001323329.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.168

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 10-48405121-A-ATG is Benign according to our data. Variant chr10-48405121-A-ATG is described in ClinVar as [Benign]. Clinvar id is 1273391.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAPK8	NM_001323329.2	c.252+141_252+142insGT		intron_variant		ENST00000374189.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAPK8	ENST00000374189.6	c.252+141_252+142insGT		intron_variant		5	NM_001323329.2	A1

Frequencies

GnomAD3 genomes AF: 0.0903 AC: 13597 AN: 150528 Hom.: 693 Cov.: 29

Gnomad AFR AF: 0.0510

Gnomad AMI AF: 0.241

Gnomad AMR AF: 0.0679

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.0593

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.103

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.0837

GnomAD4 exome AF: 0.132 AC: 15793 AN: 119474 Hom.: 1088 AF XY: 0.129 AC XY: 8108 AN XY: 62934

Gnomad4 AFR exome AF: 0.0624

Gnomad4 AMR exome AF: 0.0710

Gnomad4 ASJ exome AF: 0.119

Gnomad4 EAS exome AF: 0.0641

Gnomad4 SAS exome AF: 0.152

Gnomad4 FIN exome AF: 0.169

Gnomad4 NFE exome AF: 0.142

Gnomad4 OTH exome AF: 0.129

GnomAD4 genome AF: 0.0903 AC: 13599 AN: 150626 Hom.: 693 Cov.: 29 AF XY: 0.0912 AC XY: 6708 AN XY: 73564

Gnomad4 AFR AF: 0.0511

Gnomad4 AMR AF: 0.0678

Gnomad4 ASJ AF: 0.105

Gnomad4 EAS AF: 0.0590

Gnomad4 SAS AF: 0.102

Gnomad4 FIN AF: 0.142

Gnomad4 NFE AF: 0.111

Gnomad4 OTH AF: 0.0833

Alfa AF: 0.0367 Hom.: 25

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: rs67126940; hg19: chr10-49613164;