Genetic Variant MAPK8:c.252+141_252+142insCT (chr10-48405121-A-ATC) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001323329.2(MAPK8):c.252+141_252+142insCT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000074 in 270,242 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 29)

Exomes 𝑓: 0.0000084 ( 0 hom. )

Consequence

MAPK8
NM_001323329.2 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.168

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001323329.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MAPK8	NM_001323329.2	MANE Select	c.252+141_252+142insCT	intron	N/A	NP_001310258.1	P45983-1
MAPK8	NM_001278547.2		c.252+141_252+142insCT	intron	N/A	NP_001265476.1	A1L4K2
MAPK8	NM_001323322.2		c.252+141_252+142insCT	intron	N/A	NP_001310251.1	P45983-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MAPK8	ENST00000374189.6	TSL:5 MANE Select	c.252+140_252+141insTC	intron	N/A	ENSP00000363304.1	P45983-1
MAPK8	ENST00000374176.8	TSL:1	c.252+140_252+141insTC	intron	N/A	ENSP00000363291.4	P45983-4
MAPK8	ENST00000374179.8	TSL:1	c.252+140_252+141insTC	intron	N/A	ENSP00000363294.3	P45983-3

Frequencies

GnomAD3 genomes

AF:

0.00000664

AC:

AN:

150546

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000243

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000835

AC:

AN:

119696

Hom.:

AF XY:

0.0000159

AC XY:

AN XY:

63040

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

3894

American (AMR)

AF:

0.00

AC:

AN:

4190

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

4000

East Asian (EAS)

AF:

0.000103

AC:

AN:

9704

South Asian (SAS)

AF:

0.00

AC:

AN:

1348

European-Finnish (FIN)

AF:

0.00

AC:

AN:

12786

Middle Eastern (MID)

AF:

0.00

AC:

AN:

512

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

75840

Other (OTH)

AF:

0.00

AC:

AN:

7422

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.675

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000664

AC:

AN:

150546

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73466

show subpopulations

African (AFR)

AF:

0.0000243

AC:

AN:

41148

American (AMR)

AF:

0.00

AC:

AN:

15154

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3462

East Asian (EAS)

AF:

0.00

AC:

AN:

5164

South Asian (SAS)

AF:

0.00

AC:

AN:

4788

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9928

Middle Eastern (MID)

AF:

0.00

AC:

AN:

310

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67612

Other (OTH)

AF:

0.00

AC:

AN:

2070

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.17

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over