3-50612068-A-T

Variant names:

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

Variant summary

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

The NM_001243926.2(MAPKAPK3):​c.-436A>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.791 in 193,492 control chromosomes in the GnomAD database, including 61,924 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as risk factor (no stars).

• Frequency:
  • Genomes: 𝑓 0.78 (47092 hom., cov: 34)
  • Exomes 𝑓: 0.84 (14832 hom.)
• Consequence: MAPKAPK3 NM_001243926.2 5_prime_UTR
• Clinical Significance: risk factor no assertion criteria provided O:3
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.865 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001243926.2. 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_001243926.2		c.-436A>T		5_prime_UTR	Exon 1 of 13	NP_001230855.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPKAPK3	ENST00000446044.5	TSL:1	c.-436A>T		5_prime_UTR	Exon 1 of 13	ENSP00000396467.1
	MAPKAPK3	ENST00000864518.1		c.-53+331A>T		intron	N/A	ENSP00000534577.1
	MAPKAPK3	ENST00000969054.1		c.-375+331A>T		intron	N/A	ENSP00000639113.1

Frequencies

GnomAD3 genomes AF: 0.777 AC: 118178 AN: 152104 Hom.: 47095 Cov.: 34

Gnomad AFR AF: 0.635

Gnomad AMI AF: 0.878

Gnomad AMR AF: 0.652

Gnomad ASJ AF: 0.923

Gnomad EAS AF: 0.614

Gnomad SAS AF: 0.887

Gnomad FIN AF: 0.880

Gnomad MID AF: 0.896

Gnomad NFE AF: 0.869

Gnomad OTH AF: 0.809

GnomAD4 exome AF: 0.843 AC: 34789 AN: 41270 Hom.: 14832 Cov.: 0 AF XY: 0.848 AC XY: 17710 AN XY: 20876

African (AFR) AF: 0.647 AC: 944 AN: 1460

American (AMR) AF: 0.652 AC: 593 AN: 910

Ashkenazi Jewish (ASJ) AF: 0.926 AC: 1729 AN: 1868

East Asian (EAS) AF: 0.614 AC: 2144 AN: 3492

South Asian (SAS) AF: 0.908 AC: 1580 AN: 1740

European-Finnish (FIN) AF: 0.872 AC: 1876 AN: 2152

Middle Eastern (MID) AF: 0.885 AC: 207 AN: 234

European-Non Finnish (NFE) AF: 0.878 AC: 23290 AN: 26514

Other (OTH) AF: 0.837 AC: 2426 AN: 2900

GnomAD4 genome AF: 0.777 AC: 118206 AN: 152222 Hom.: 47092 Cov.: 34 AF XY: 0.775 AC XY: 57716 AN XY: 74434

African (AFR) AF: 0.634 AC: 26352 AN: 41532

American (AMR) AF: 0.652 AC: 9982 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.923 AC: 3204 AN: 3472

East Asian (EAS) AF: 0.615 AC: 3171 AN: 5160

South Asian (SAS) AF: 0.887 AC: 4278 AN: 4824

European-Finnish (FIN) AF: 0.880 AC: 9337 AN: 10608

Middle Eastern (MID) AF: 0.895 AC: 263 AN: 294

European-Non Finnish (NFE) AF: 0.869 AC: 59110 AN: 68000

Other (OTH) AF: 0.808 AC: 1710 AN: 2116

Alfa AF: 0.810 Hom.: 5988

Bravo AF: 0.751

Asia WGS AF: 0.752 AC: 2613 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: risk factor

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	-	Bacteremia, susceptibility to, 2 (1)
-	-	-	Malaria, susceptibility to (1)
-	-	-	Tuberculosis, susceptibility to (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	16
DANN	Benign	0.56
PhyloP100		2.4
PromoterAI		0.039	Neutral
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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;