rs77211491

Variant names:

• chr12-111884974-G-A
• rs77211491
• NM_003668.4:c.849-942G>A

Variant summary

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

The NM_003668.4(MAPKAPK5):​c.849-942G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0919 in 152,216 control chromosomes in the GnomAD database, including 702 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 0.092 (702 hom., cov: 32)
• Consequence: MAPKAPK5 NM_003668.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.01
• Publications: 5 publications found

Genes affected

MAPKAPK5 (HGNC:6889): (MAPK activated protein kinase 5) The protein encoded by this gene is a tumor suppressor and member of the serine/threonine kinase family. In response to cellular stress and proinflammatory cytokines, this kinase is activated through its phosphorylation by MAP kinases including MAPK1/ERK, MAPK14/p38-alpha, and MAPK11/p38-beta. The encoded protein is found in the nucleus but translocates to the cytoplasm upon phosphorylation and activation. This kinase phosphorylates heat shock protein HSP27 at its physiologically relevant sites. Two alternately spliced transcript variants of this gene encoding distinct isoforms have been reported. [provided by RefSeq, Nov 2012]

MAPKAPK5 Gene-Disease associations (from GenCC):

• neurocardiofaciodigital syndrome

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAPKAPK5	NM_003668.4	c.849-942G>A		intron_variant	Intron 9 of 13	ENST00000550735.7	NP_003659.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAPKAPK5	ENST00000550735.7	c.849-942G>A		intron_variant	Intron 9 of 13	1	NM_003668.4	ENSP00000449667.2
MAPKAPK5	ENST00000551404.7	c.849-942G>A		intron_variant	Intron 9 of 13	5		ENSP00000449381.2
MAPKAPK5	ENST00000549875.1	c.402-942G>A		intron_variant	Intron 4 of 8	5		ENSP00000473467.1
MAPKAPK5	ENST00000553053.5	n.*241-942G>A		intron_variant	Intron 5 of 6	5		ENSP00000448408.2

Frequencies

GnomAD3 genomes AF: 0.0920 AC: 13992 AN: 152096 Hom.: 702 Cov.: 32

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.0564

Gnomad ASJ AF: 0.0256

Gnomad EAS AF: 0.228

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.0987

Gnomad NFE AF: 0.0791

Gnomad OTH AF: 0.0837

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0919 AC: 13996 AN: 152216 Hom.: 702 Cov.: 32 AF XY: 0.0930 AC XY: 6924 AN XY: 74416

African (AFR) AF: 0.109 AC: 4522 AN: 41540

American (AMR) AF: 0.0563 AC: 861 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0256 AC: 89 AN: 3470

East Asian (EAS) AF: 0.228 AC: 1181 AN: 5170

South Asian (SAS) AF: 0.138 AC: 665 AN: 4824

European-Finnish (FIN) AF: 0.101 AC: 1074 AN: 10596

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0792 AC: 5386 AN: 68008

Other (OTH) AF: 0.0824 AC: 174 AN: 2112

Alfa AF: 0.0920 Hom.: 219

Bravo AF: 0.0906

Asia WGS AF: 0.215 AC: 747 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.6
DANN	Benign	0.60
PhyloP100		1.0
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: rs77211491; hg19: chr12-112322778;