chr3-50612068-A-T

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

2

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]

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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 HGVSp Effect #exon/exons MANE Protein UniProt
MAPKAPK3NM_001243926.2 linkuse as main transcriptc.-436A>T 5_prime_UTR_variant 1/13 NP_001230855.1
MAPKAPK3XM_047448883.1 linkuse as main transcriptc.-436A>T 5_prime_UTR_variant 2/14 XP_047304839.1
MAPKAPK3XM_047448887.1 linkuse as main transcriptc.-375+331A>T intron_variant XP_047304843.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MAPKAPK3ENST00000446044.5 linkuse as main transcriptc.-436A>T 5_prime_UTR_variant 1/131 ENSP00000396467 P1
MAPKAPK3ENST00000486712.5 linkuse as main transcriptn.293A>T non_coding_transcript_exon_variant 2/44

Frequencies

GnomAD3 genomes
AF:
0.777
AC:
118178
AN:
152104
Hom.:
47095
Cov.:
34
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.:
0
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.:
34
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 providedliterature onlyOMIMJun 03, 2010- -
Malaria, susceptibility to Other:1
risk factor, no assertion criteria providedliterature onlyOMIMJun 03, 2010- -
Tuberculosis, susceptibility to Other:1
risk factor, no assertion criteria providedliterature onlyOMIMJun 03, 2010- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.77
CADD
Benign
16
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.

Other links and lift over

dbSNP: rs414171; hg19: chr3-50649499; API