chr3-50648767-A-C

Position:

• chr3-50648767-A-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAPKAPK3	NM_001243925.2	c.*721A>C		3_prime_UTR_variant	11/11	ENST00000621469.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAPKAPK3	ENST00000621469.5	c.*721A>C		3_prime_UTR_variant	11/11	1	NM_001243925.2	P1
MAPKAPK3	ENST00000357955.6	c.*721A>C		3_prime_UTR_variant	11/11	1		P1
MAPKAPK3	ENST00000446044.5	c.*721A>C		3_prime_UTR_variant	13/13	1		P1

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

Gnomad4 ASJ exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0500

Gnomad4 OTH exome AF: 0.250

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

Gnomad4 AFR AF: 0.0231

Gnomad4 AMR AF: 0.0707

Gnomad4 ASJ AF: 0.0386

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0147

Gnomad4 FIN AF: 0.133

Gnomad4 NFE AF: 0.121

Gnomad4 OTH AF: 0.0739

Alfa AF: 0.104 Hom.: 1279

Bravo AF: 0.0728

Asia WGS AF: 0.0120 AC: 43 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.4
DANN	Benign	0.51

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

Publications

LitVar

Other links and lift over

dbSNP: rs11130254; hg19: chr3-50686198;