3-50613461-G-C

Variant names:

• chr3-50613461-G-C
• rs809451
• ENST00000446044.5:c.-279-331G>C

Variant summary

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

The ENST00000446044.5(MAPKAPK3):​c.-279-331G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.85 in 152,178 control chromosomes in the GnomAD database, including 55,386 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 (55386 hom., cov: 32)
• Consequence: MAPKAPK3 ENST00000446044.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.579
• Publications: 11 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.923 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000446044.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPKAPK3	NM_001243926.2		c.-279-331G>C		intron	N/A	NP_001230855.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPKAPK3	ENST00000446044.5	TSL:1	c.-279-331G>C		intron	N/A	ENSP00000396467.1
	MAPKAPK3	ENST00000486712.5	TSL:4	n.450-331G>C		intron	N/A
	MAPKAPK3	ENST00000497283.1	TSL:2	n.468-331G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.851 AC: 129352 AN: 152060 Hom.: 55376 Cov.: 32

Gnomad AFR AF: 0.759

Gnomad AMI AF: 0.878

Gnomad AMR AF: 0.872

Gnomad ASJ AF: 0.940

Gnomad EAS AF: 0.945

Gnomad SAS AF: 0.916

Gnomad FIN AF: 0.882

Gnomad MID AF: 0.911

Gnomad NFE AF: 0.879

Gnomad OTH AF: 0.873

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

GnomAD4 genome AF: 0.850 AC: 129407 AN: 152178 Hom.: 55386 Cov.: 32 AF XY: 0.852 AC XY: 63424 AN XY: 74416

African (AFR) AF: 0.758 AC: 31457 AN: 41482

American (AMR) AF: 0.872 AC: 13332 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.940 AC: 3260 AN: 3468

East Asian (EAS) AF: 0.946 AC: 4902 AN: 5184

South Asian (SAS) AF: 0.916 AC: 4417 AN: 4824

European-Finnish (FIN) AF: 0.882 AC: 9351 AN: 10606

Middle Eastern (MID) AF: 0.912 AC: 268 AN: 294

European-Non Finnish (NFE) AF: 0.879 AC: 59779 AN: 68006

Other (OTH) AF: 0.871 AC: 1840 AN: 2112

Alfa AF: 0.811 Hom.: 2572

Bravo AF: 0.846

Asia WGS AF: 0.893 AC: 3102 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.26
DANN	Benign	0.40
PhyloP100		-0.58
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: rs809451; hg19: chr3-50650892;