rs616589

Variant names:

• chr3-50626198-A-G
• rs616589
• NM_001243925.2:c.219+8414A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001243925.2(MAPKAPK3):​c.219+8414A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.775 in 151,912 control chromosomes in the GnomAD database, including 46,911 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 0.78 (46911 hom., cov: 30)
• Consequence: MAPKAPK3 NM_001243925.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.603
• Publications: 2 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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.868 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAPKAPK3	NM_001243925.2	c.219+8414A>G		intron_variant	Intron 2 of 10	ENST00000621469.5	NP_001230854.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAPKAPK3	ENST00000621469.5	c.219+8414A>G		intron_variant	Intron 2 of 10	1	NM_001243925.2	ENSP00000478922.1

Frequencies

GnomAD3 genomes AF: 0.776 AC: 117771 AN: 151794 Hom.: 46915 Cov.: 30

Gnomad AFR AF: 0.628

Gnomad AMI AF: 0.878

Gnomad AMR AF: 0.652

Gnomad ASJ AF: 0.923

Gnomad EAS AF: 0.632

Gnomad SAS AF: 0.891

Gnomad FIN AF: 0.880

Gnomad MID AF: 0.896

Gnomad NFE AF: 0.870

Gnomad OTH AF: 0.811

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

GnomAD4 genome AF: 0.775 AC: 117797 AN: 151912 Hom.: 46911 Cov.: 30 AF XY: 0.775 AC XY: 57508 AN XY: 74246

African (AFR) AF: 0.627 AC: 25915 AN: 41348

American (AMR) AF: 0.652 AC: 9956 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.923 AC: 3205 AN: 3472

East Asian (EAS) AF: 0.633 AC: 3254 AN: 5144

South Asian (SAS) AF: 0.890 AC: 4291 AN: 4820

European-Finnish (FIN) AF: 0.880 AC: 9306 AN: 10572

Middle Eastern (MID) AF: 0.895 AC: 263 AN: 294

European-Non Finnish (NFE) AF: 0.870 AC: 59099 AN: 67968

Other (OTH) AF: 0.810 AC: 1707 AN: 2108

Alfa AF: 0.803 Hom.: 6484

Bravo AF: 0.750

Asia WGS AF: 0.761 AC: 2645 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.32
DANN	Benign	0.32
PhyloP100		-0.60
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs616589; hg19: chr3-50663629;