NM_001243925.2:c.*721A>C

Variant names:

• chr3-50648767-A-C
• rs11130254
• NM_001243925.2:c.*721A>C

Variant summary

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

The NM_001243925.2(MAPKAPK3):​c.*721A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0801 in 152,320 control chromosomes in the GnomAD database, including 682 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 0.080 (682 hom., cov: 34)
  • Exomes 𝑓: 0.059 (0 hom.)
• Consequence: MAPKAPK3 NM_001243925.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.912
• Publications: 20 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPKAPK3	NM_001243925.2	MANE Select	c.*721A>C		3_prime_UTR	Exon 11 of 11	NP_001230854.1
	MAPKAPK3	NM_001243926.2		c.*721A>C		3_prime_UTR	Exon 13 of 13	NP_001230855.1
	MAPKAPK3	NM_004635.5		c.*721A>C		3_prime_UTR	Exon 11 of 11	NP_004626.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPKAPK3	ENST00000621469.5	TSL:1 MANE Select	c.*721A>C		3_prime_UTR	Exon 11 of 11	ENSP00000478922.1
	MAPKAPK3	ENST00000357955.6	TSL:1	c.*721A>C		3_prime_UTR	Exon 11 of 11	ENSP00000350639.2
	MAPKAPK3	ENST00000446044.5	TSL:1	c.*721A>C		3_prime_UTR	Exon 13 of 13	ENSP00000396467.1

Frequencies

GnomAD3 genomes AF: 0.0802 AC: 12200 AN: 152168 Hom.: 682 Cov.: 34

Gnomad AFR AF: 0.0232

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.0707

Gnomad ASJ AF: 0.0386

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0145

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.0747

GnomAD4 exome AF: 0.0588 AC: 2 AN: 34 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 24

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.0500 AC: 1 AN: 20

Other (OTH) AF: 0.250 AC: 1 AN: 4

GnomAD4 genome AF: 0.0801 AC: 12201 AN: 152286 Hom.: 682 Cov.: 34 AF XY: 0.0797 AC XY: 5934 AN XY: 74454

African (AFR) AF: 0.0231 AC: 960 AN: 41582

American (AMR) AF: 0.0707 AC: 1082 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0386 AC: 134 AN: 3468

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5182

South Asian (SAS) AF: 0.0147 AC: 71 AN: 4820

European-Finnish (FIN) AF: 0.133 AC: 1408 AN: 10606

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.121 AC: 8243 AN: 68012

Other (OTH) AF: 0.0739 AC: 156 AN: 2110

Alfa AF: 0.101 Hom.: 1574

Bravo AF: 0.0728

Asia WGS AF: 0.0120 AC: 43 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.4
DANN	Benign	0.51
PhyloP100		0.91
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: rs11130254; hg19: chr3-50686198;