NM_001243925.2:c.69C>T

Variant names:

• chr3-50617634-C-T
• rs2032504265
• NM_001243925.2:c.69C>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_001243925.2(MAPKAPK3):​c.69C>T​(p.Gly23Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,456,470 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: MAPKAPK3 NM_001243925.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.358
• Publications: 0 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: Orphanet, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 3-50617634-C-T is Benign according to our data. Variant chr3-50617634-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1041290.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.358 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001243925.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPKAPK3	NM_001243925.2	MANE Select	c.69C>T	p.Gly23Gly	synonymous	Exon 2 of 11	NP_001230854.1	Q16644
	MAPKAPK3	NM_001243926.2		c.69C>T	p.Gly23Gly	synonymous	Exon 4 of 13	NP_001230855.1	Q16644
	MAPKAPK3	NM_004635.5		c.69C>T	p.Gly23Gly	synonymous	Exon 2 of 11	NP_004626.1	Q16644

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPKAPK3	ENST00000621469.5	TSL:1 MANE Select	c.69C>T	p.Gly23Gly	synonymous	Exon 2 of 11	ENSP00000478922.1	Q16644
	MAPKAPK3	ENST00000357955.6	TSL:1	c.69C>T	p.Gly23Gly	synonymous	Exon 2 of 11	ENSP00000350639.2	Q16644
	MAPKAPK3	ENST00000446044.5	TSL:1	c.69C>T	p.Gly23Gly	synonymous	Exon 4 of 13	ENSP00000396467.1	Q16644

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1456470 Hom.: 0 Cov.: 29 AF XY: 0.00000276 AC XY: 2 AN XY: 724604

African (AFR) AF: 0.00 AC: 0 AN: 33416

American (AMR) AF: 0.00 AC: 0 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26098

East Asian (EAS) AF: 0.00 AC: 0 AN: 39676

South Asian (SAS) AF: 0.00 AC: 0 AN: 86150

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52584

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5350

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1108330

Other (OTH) AF: 0.0000166 AC: 1 AN: 60156

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000312 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	7.5
DANN	Benign	0.84
PhyloP100		0.36
PromoterAI		0.033	Neutral

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: rs2032504265; hg19: chr3-50655065;