3-50612068-A-G

Variant names:

• chr3-50612068-A-G
• rs414171
• ENST00000446044.5:c.-436A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000446044.5(MAPKAPK3):​c.-436A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 34)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MAPKAPK3 ENST00000446044.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.42
• Publications: 24 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).

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.-436A>G		5_prime_UTR	Exon 1 of 13	NP_001230855.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPKAPK3	ENST00000446044.5	TSL:1	c.-436A>G		5_prime_UTR	Exon 1 of 13	ENSP00000396467.1
	MAPKAPK3	ENST00000486712.5	TSL:4	n.293A>G		non_coding_transcript_exon	Exon 2 of 4

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 41344 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 20914

African (AFR) AF: 0.00 AC: 0 AN: 1470

American (AMR) AF: 0.00 AC: 0 AN: 910

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1868

East Asian (EAS) AF: 0.00 AC: 0 AN: 3502

South Asian (SAS) AF: 0.00 AC: 0 AN: 1740

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2158

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 234

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 26552

Other (OTH) AF: 0.00 AC: 0 AN: 2910

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 5988

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	18
DANN	Benign	0.49
PhyloP100		2.4
PromoterAI		-0.0084	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: rs414171; hg19: chr3-50649499;