3-50611939-C-G

Position:

• chr3-50611939-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001243926.2(MAPKAPK3):​c.-565C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.876 in 427,370 control chromosomes in the GnomAD database, including 164,583 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.85 (55408 hom., cov: 38)
  • Exomes 𝑓: 0.89 (109175 hom.)
• Consequence: MAPKAPK3 NM_001243926.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.332

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.923 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAPKAPK3	NM_001243926.2	c.-565C>G		5_prime_UTR_variant	1/13		NP_001230855.1
MAPKAPK3	XM_047448883.1	c.-510-55C>G		intron_variant			XP_047304839.1
MAPKAPK3	XM_047448887.1	c.-375+202C>G		intron_variant			XP_047304843.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAPKAPK3	ENST00000446044	c.-565C>G		5_prime_UTR_variant	1/13	1		ENSP00000396467.1
MAPKAPK3	ENST00000486712.5	n.219-55C>G		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.851 AC: 129426 AN: 152140 Hom.: 55398 Cov.: 38

Gnomad AFR AF: 0.760

Gnomad AMI AF: 0.878

Gnomad AMR AF: 0.872

Gnomad ASJ AF: 0.940

Gnomad EAS AF: 0.945

Gnomad SAS AF: 0.917

Gnomad FIN AF: 0.882

Gnomad MID AF: 0.914

Gnomad NFE AF: 0.879

Gnomad OTH AF: 0.874

GnomAD4 exome AF: 0.890 AC: 244880 AN: 275114 Hom.: 109175 Cov.: 4 AF XY: 0.891 AC XY: 126161 AN XY: 141630

Gnomad4 AFR exome AF: 0.761

Gnomad4 AMR exome AF: 0.881

Gnomad4 ASJ exome AF: 0.942

Gnomad4 EAS exome AF: 0.944

Gnomad4 SAS exome AF: 0.932

Gnomad4 FIN exome AF: 0.876

Gnomad4 NFE exome AF: 0.885

Gnomad4 OTH exome AF: 0.886

GnomAD4 genome AF: 0.850 AC: 129480 AN: 152256 Hom.: 55408 Cov.: 38 AF XY: 0.852 AC XY: 63468 AN XY: 74456

Gnomad4 AFR AF: 0.759

Gnomad4 AMR AF: 0.872

Gnomad4 ASJ AF: 0.940

Gnomad4 EAS AF: 0.945

Gnomad4 SAS AF: 0.916

Gnomad4 FIN AF: 0.882

Gnomad4 NFE AF: 0.879

Gnomad4 OTH AF: 0.872

Alfa AF: 0.851 Hom.: 6900

Bravo AF: 0.846

Asia WGS AF: 0.892 AC: 3097 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	9.1
DANN	Benign	0.67

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

Other links and lift over

dbSNP: rs6768300; hg19: chr3-50649370;