chr3-50612068-A-T

Variant names:

• chr3-50612068-A-T
• rs414171
• ENST00000446044: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

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

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAPKAPK3	NM_001243926.2	c.-436A>T		5_prime_UTR_variant	Exon 1 of 13		NP_001230855.1
MAPKAPK3	XM_047448883.1	c.-436A>T		5_prime_UTR_variant	Exon 2 of 14		XP_047304839.1
MAPKAPK3	XM_047448887.1	c.-375+331A>T		intron_variant	Intron 1 of 12		XP_047304843.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAPKAPK3	ENST00000446044	c.-436A>T		5_prime_UTR_variant	Exon 1 of 13	1		ENSP00000396467.1
MAPKAPK3	ENST00000486712.5	n.293A>T		non_coding_transcript_exon_variant	Exon 2 of 4	4

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

Gnomad4 AFR exome AF: 0.647 AC: 944 AN: 1460

Gnomad4 AMR exome AF: 0.652 AC: 593 AN: 910

Gnomad4 ASJ exome AF: 0.926 AC: 1729 AN: 1868

Gnomad4 EAS exome AF: 0.614 AC: 2144 AN: 3492

Gnomad4 SAS exome AF: 0.908 AC: 1580 AN: 1740

Gnomad4 FIN exome AF: 0.872 AC: 1876 AN: 2152

Gnomad4 NFE exome AF: 0.878 AC: 23290 AN: 26514

Gnomad4 Remaining exome 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

Gnomad4 AFR AF: 0.634 AC: 0.634499 AN: 0.634499

Gnomad4 AMR AF: 0.652 AC: 0.652163 AN: 0.652163

Gnomad4 ASJ AF: 0.923 AC: 0.922811 AN: 0.922811

Gnomad4 EAS AF: 0.615 AC: 0.614535 AN: 0.614535

Gnomad4 SAS AF: 0.887 AC: 0.886816 AN: 0.886816

Gnomad4 FIN AF: 0.880 AC: 0.880185 AN: 0.880185

Gnomad4 NFE AF: 0.869 AC: 0.869265 AN: 0.869265

Gnomad4 OTH AF: 0.808 AC: 0.808129 AN: 0.808129

Alfa AF: 0.810 Hom.: 5988

Bravo AF: 0.751

Asia WGS AF: 0.752 AC: 2613 AN: 3478

ClinVar

Significance: risk factor

Submissions summary: Other:3

Revision: no assertion criteria provided

Submissions by phenotype

Bacteremia, susceptibility to, 2 Other:1

Jun 03, 2010

OMIM

Significance: risk factor

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Malaria, susceptibility to Other:1

Jun 03, 2010

OMIM

Significance: risk factor

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Tuberculosis, susceptibility to Other:1

Jun 03, 2010

OMIM

Significance: risk factor

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	16
DANN	Benign	0.56
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

Publications

LitVar

Other links and lift over

dbSNP: rs414171; hg19: chr3-50649499;