rs3792323

Variant names:

• chr3-50622900-A-T
• rs3792323
• NM_001243925.2:c.219+5116A>T

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+5116A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0564 in 152,278 control chromosomes in the GnomAD database, including 877 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 0.056 (877 hom., cov: 32)
• Consequence: MAPKAPK3 NM_001243925.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.430
• Publications: 3 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 = 0.318 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAPKAPK3	NM_001243925.2	c.219+5116A>T		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+5116A>T		intron_variant	Intron 2 of 10	1	NM_001243925.2	ENSP00000478922.1

Frequencies

GnomAD3 genomes AF: 0.0565 AC: 8590 AN: 152160 Hom.: 875 Cov.: 32

Gnomad AFR AF: 0.0810

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.00836

Gnomad EAS AF: 0.331

Gnomad SAS AF: 0.0279

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00116

Gnomad OTH AF: 0.0449

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

GnomAD4 genome AF: 0.0564 AC: 8596 AN: 152278 Hom.: 877 Cov.: 32 AF XY: 0.0603 AC XY: 4490 AN XY: 74464

African (AFR) AF: 0.0809 AC: 3362 AN: 41550

American (AMR) AF: 0.208 AC: 3186 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00836 AC: 29 AN: 3470

East Asian (EAS) AF: 0.331 AC: 1711 AN: 5168

South Asian (SAS) AF: 0.0278 AC: 134 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00116 AC: 79 AN: 68030

Other (OTH) AF: 0.0440 AC: 93 AN: 2114

Alfa AF: 0.0278 Hom.: 62

Bravo AF: 0.0756

Asia WGS AF: 0.133 AC: 461 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.4
DANN	Benign	0.79
PhyloP100		0.43
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: rs3792323; hg19: chr3-50660331;