rs873985

Positions:

• chr3-50614320-A-G

Variant summary

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

The ENST00000446044.5(MAPKAPK3):​c.-53+302A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 152,112 control chromosomes in the GnomAD database, including 1,329 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 0.12 (1329 hom., cov: 32)
• Consequence: MAPKAPK3 ENST00000446044.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.416

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAPKAPK3	NM_001243926.2	c.-53+302A>G		intron_variant			NP_001230855.1
MAPKAPK3	XM_047448883.1	c.-53+302A>G		intron_variant			XP_047304839.1
MAPKAPK3	XM_047448884.1	c.-53+302A>G		intron_variant			XP_047304840.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAPKAPK3	ENST00000446044.5	c.-53+302A>G		intron_variant		1		ENSP00000396467	P1

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17784 AN: 151994 Hom.: 1329 Cov.: 32

Gnomad AFR AF: 0.0314

Gnomad AMI AF: 0.188

Gnomad AMR AF: 0.0922

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.00847

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.238

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.119

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.117 AC: 17783 AN: 152112 Hom.: 1329 Cov.: 32 AF XY: 0.120 AC XY: 8932 AN XY: 74346

Gnomad4 AFR AF: 0.0314

Gnomad4 AMR AF: 0.0921

Gnomad4 ASJ AF: 0.173

Gnomad4 EAS AF: 0.00830

Gnomad4 SAS AF: 0.164

Gnomad4 FIN AF: 0.238

Gnomad4 NFE AF: 0.157

Gnomad4 OTH AF: 0.117

Alfa AF: 0.142 Hom.: 1821

Bravo AF: 0.102

Asia WGS AF: 0.0860 AC: 299 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.2
DANN	Benign	0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs873985; hg19: chr3-50651751;