Variant 10-48427029-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.461

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 -20 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_multiple_submitters_no_conflicts, 2 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 linkuse as main transcript	c.997-51T>A		intron_variant		ENST00000374189.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAPK8	ENST00000374189.6 linkuse as main transcript	c.997-51T>A		intron_variant		5	NM_001323329.2	A1	P45983-1

Frequencies

GnomAD3 genomes

AF:

0.0437

AC:

6655

AN:

152166

Hom.:

168

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.0362

AC XY:

22371

AN XY:

617270

show subpopulations

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.:

AF XY:

0.0418

AC XY:

3110

AN XY:

74462

show subpopulations

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.:

Bravo

AF:

0.0446

Asia WGS

AF:

0.00867

AC:

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 22, 2021	- -

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

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