Variant 10-48427234-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001323329.2(MAPK8):c.1060+91T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0647 in 857,448 control chromosomes in the GnomAD database, including 3,474 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.062 ( 624 hom., cov: 32)

Exomes 𝑓: 0.065 ( 2850 hom. )

Consequence

MAPK8
NM_001323329.2 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.204

Variant links:

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]

MAPK8 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 10-48427234-T-G is Benign according to our data. Variant chr10-48427234-T-G is described in ClinVar as [Benign]. Clinvar id is 2688199.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAPK8	NM_001323329.2 linkuse as main transcript	c.1060+91T>G		intron_variant		ENST00000374189.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAPK8	ENST00000374189.6 linkuse as main transcript	c.1060+91T>G		intron_variant		5	NM_001323329.2	A1	P45983-1

Frequencies

GnomAD3 genomes

AF:

0.0618

AC:

9398

AN:

152178

Hom.:

624

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0295

Gnomad AMI

AF:

0.0570

Gnomad AMR

AF:

0.213

Gnomad ASJ

AF:

0.0657

Gnomad EAS

AF:

0.0273

Gnomad SAS

AF:

0.163

Gnomad FIN

AF:

0.0415

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0460

Gnomad OTH

AF:

0.0636

GnomAD4 exome

AF:

0.0653

AC:

46076

AN:

705152

Hom.:

2850

Cov.:

AF XY:

0.0683

AC XY:

25277

AN XY:

370036

show subpopulations

Gnomad4 AFR exome

AF:

0.0283

Gnomad4 AMR exome

AF:

0.262

Gnomad4 ASJ exome

AF:

0.0702

Gnomad4 EAS exome

AF:

0.0156

Gnomad4 SAS exome

AF:

0.162

Gnomad4 FIN exome

AF:

0.0460

Gnomad4 NFE exome

AF:

0.0463

Gnomad4 OTH exome

AF:

0.0636

GnomAD4 genome

AF:

0.0618

AC:

9414

AN:

152296

Hom.:

624

Cov.:

AF XY:

0.0667

AC XY:

4966

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.0295

Gnomad4 AMR

AF:

0.213

Gnomad4 ASJ

AF:

0.0657

Gnomad4 EAS

AF:

0.0274

Gnomad4 SAS

AF:

0.163

Gnomad4 FIN

AF:

0.0415

Gnomad4 NFE

AF:

0.0461

Gnomad4 OTH

AF:

0.0662

Alfa

AF:

0.0278

Hom.:

Bravo

AF:

0.0693

Asia WGS

AF:

0.120

AC:

417

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 36% of patients studied by a panel of primary immunodeficiencies. Number of patients: 34. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.17

DANN

Benign

0.52

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over