chr3-50614320-A-G

Variant names:

• chr3-50614320-A-G
• rs873985
• ENST00000446044.5:c.-53+302A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 publications found

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 Gene-Disease associations (from GenCC):

• patterned macular dystrophy 3

  Inheritance: AD, Unknown Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
MAPKAPK3	NM_001243926.2	c.-53+302A>G		intron_variant	Intron 3 of 12		NP_001230855.1
MAPKAPK3	XM_047448883.1	c.-53+302A>G		intron_variant	Intron 4 of 13		XP_047304839.1
MAPKAPK3	XM_047448884.1	c.-53+302A>G		intron_variant	Intron 3 of 12		XP_047304840.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAPKAPK3	ENST00000446044.5	c.-53+302A>G		intron_variant	Intron 3 of 12	1		ENSP00000396467.1
MAPKAPK3	ENST00000497283.1	n.*203A>G		downstream_gene_variant		2

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

African (AFR) AF: 0.0314 AC: 1301 AN: 41496

American (AMR) AF: 0.0921 AC: 1408 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.173 AC: 600 AN: 3470

East Asian (EAS) AF: 0.00830 AC: 43 AN: 5180

South Asian (SAS) AF: 0.164 AC: 792 AN: 4822

European-Finnish (FIN) AF: 0.238 AC: 2511 AN: 10562

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.157 AC: 10665 AN: 67976

Other (OTH) AF: 0.117 AC: 248 AN: 2114

Alfa AF: 0.137 Hom.: 2497

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
PhyloP100		0.42
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs873985; hg19: chr3-50651751;