Variant 3-50612068-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000446044.5(MAPKAPK3):c.-436A>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.791 in 193,492 control chromosomes in the GnomAD database, including 61,924 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as risk factor (no stars).

Frequency

Genomes: 𝑓 0.78 ( 47092 hom., cov: 34)

Exomes 𝑓: 0.84 ( 14832 hom. )

Consequence

MAPKAPK3
ENST00000446044.5 5_prime_UTR

Scores

Clinical Significance

risk factor no assertion criteria provided O:3

Conservation

PhyloP100: 2.42

Variant links:

Genes affected

MAPKAPK3 (HGNC:6888): (MAPK activated protein kinase 3) This gene encodes a member of the Ser/Thr protein kinase family. This kinase functions as a mitogen-activated protein kinase (MAP kinase)- activated protein kinase. MAP kinases are also known as extracellular signal-regulated kinases (ERKs), act as an integration point for multiple biochemical signals. This kinase was shown to be activated by growth inducers and stress stimulation of cells. In vitro studies demonstrated that ERK, p38 MAP kinase and Jun N-terminal kinase were all able to phosphorylate and activate this kinase, which suggested the role of this kinase as an integrative element of signaling in both mitogen and stress responses. This kinase was reported to interact with, phosphorylate and repress the activity of E47, which is a basic helix-loop-helix transcription factor known to be involved in the regulation of tissue-specific gene expression and cell differentiation. Alternate splicing results in multiple transcript variants that encode the same protein. [provided by RefSeq, Sep 2011]

MAPKAPK3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.865 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons
MAPKAPK3	NM_001243926.2 linkuse as main transcript	c.-436A>T	5_prime_UTR_variant	1/13
MAPKAPK3	XM_047448883.1 linkuse as main transcript	c.-436A>T	5_prime_UTR_variant	2/14
MAPKAPK3	XM_047448887.1 linkuse as main transcript	c.-375+331A>T	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAPKAPK3	ENST00000446044.5 linkuse as main transcript	c.-436A>T		5_prime_UTR_variant	1/13	1		P1
MAPKAPK3	ENST00000486712.5 linkuse as main transcript	n.293A>T		non_coding_transcript_exon_variant	2/4	4

Frequencies

GnomAD3 genomes

AF:

0.777

AC:

118178

AN:

152104

Hom.:

47095

Cov.:

show subpopulations

Gnomad AFR

AF:

0.635

Gnomad AMI

AF:

0.878

Gnomad AMR

AF:

0.652

Gnomad ASJ

AF:

0.923

Gnomad EAS

AF:

0.614

Gnomad SAS

AF:

0.887

Gnomad FIN

AF:

0.880

Gnomad MID

AF:

0.896

Gnomad NFE

AF:

0.869

Gnomad OTH

AF:

0.809

GnomAD4 exome

AF:

0.843

AC:

34789

AN:

41270

Hom.:

14832

Cov.:

AF XY:

0.848

AC XY:

17710

AN XY:

20876

show subpopulations

Gnomad4 AFR exome

AF:

0.647

Gnomad4 AMR exome

AF:

0.652

Gnomad4 ASJ exome

AF:

0.926

Gnomad4 EAS exome

AF:

0.614

Gnomad4 SAS exome

AF:

0.908

Gnomad4 FIN exome

AF:

0.872

Gnomad4 NFE exome

AF:

0.878

Gnomad4 OTH exome

AF:

0.837

GnomAD4 genome

AF:

0.777

AC:

118206

AN:

152222

Hom.:

47092

Cov.:

AF XY:

0.775

AC XY:

57716

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.634

Gnomad4 AMR

AF:

0.652

Gnomad4 ASJ

AF:

0.923

Gnomad4 EAS

AF:

0.615

Gnomad4 SAS

AF:

0.887

Gnomad4 FIN

AF:

0.880

Gnomad4 NFE

AF:

0.869

Gnomad4 OTH

AF:

0.808

Alfa

AF:

0.810

Hom.:

5988

Bravo

AF:

0.751

Asia WGS

AF:

0.752

AC:

2613

AN:

3478

ClinVar

Significance: risk factor

Submissions summary: Other:3

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Bacteremia, susceptibility to, 2

Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Jun 03, 2010

- -

Malaria, susceptibility to

Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Jun 03, 2010

- -

Tuberculosis, susceptibility to

Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Jun 03, 2010

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

DANN

Benign

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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