1-206685327-C-A

Variant names:

• chr1-206685327-C-A
• rs573218643
• NM_032960.4:c.98C>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_032960.4(MAPKAPK2):​c.98C>A​(p.Ala33Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000407 in 147,380 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A33G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000041 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MAPKAPK2 NM_032960.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.906
• Publications: 1 publications found

Genes affected

MAPKAPK2 (HGNC:6887): (MAPK activated protein kinase 2) This gene encodes a member of the Ser/Thr protein kinase family. This kinase is regulated through direct phosphorylation by p38 MAP kinase. In conjunction with p38 MAP kinase, this kinase is known to be involved in many cellular processes including stress and inflammatory responses, nuclear export, gene expression regulation and cell proliferation. Heat shock protein HSP27 was shown to be one of the substrates of this kinase in vivo. Two transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.121929795).
• BS2: High AC in GnomAd4 at 6 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032960.4. 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
	MAPKAPK2	NM_032960.4	MANE Select	c.98C>A	p.Ala33Glu	missense	Exon 1 of 10	NP_116584.2
	MAPKAPK2	NM_004759.5		c.98C>A	p.Ala33Glu	missense	Exon 1 of 10	NP_004750.1	P49137-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPKAPK2	ENST00000367103.4	TSL:1 MANE Select	c.98C>A	p.Ala33Glu	missense	Exon 1 of 10	ENSP00000356070.4	P49137-1
	MAPKAPK2	ENST00000294981.8	TSL:1	c.98C>A	p.Ala33Glu	missense	Exon 1 of 10	ENSP00000294981.4	P49137-2
	MAPKAPK2	ENST00000916346.1		c.98C>A	p.Ala33Glu	missense	Exon 1 of 10	ENSP00000586405.1

Frequencies

GnomAD3 genomes AF: 0.0000407 AC: 6 AN: 147380 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.000148

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1279596 Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0 AN XY: 634776

African (AFR) AF: 0.00 AC: 0 AN: 25522

American (AMR) AF: 0.00 AC: 0 AN: 28940

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20358

East Asian (EAS) AF: 0.00 AC: 0 AN: 25168

South Asian (SAS) AF: 0.00 AC: 0 AN: 73622

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44828

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3496

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1007822

Other (OTH) AF: 0.00 AC: 0 AN: 49840

GnomAD4 genome AF: 0.0000407 AC: 6 AN: 147380 Hom.: 0 Cov.: 30 AF XY: 0.0000139 AC XY: 1 AN XY: 71850

African (AFR) AF: 0.000148 AC: 6 AN: 40620

American (AMR) AF: 0.00 AC: 0 AN: 14924

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3400

East Asian (EAS) AF: 0.00 AC: 0 AN: 5060

South Asian (SAS) AF: 0.00 AC: 0 AN: 4774

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9166

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66188

Other (OTH) AF: 0.00 AC: 0 AN: 2032

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	15
DANN	Benign	0.95
DEOGEN2	Benign	0.094	T
Eigen	Benign	-0.98
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.43	T
M_CAP	Pathogenic	0.42	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
PhyloP100		0.91
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	0.24	N
REVEL	Benign	0.023
Sift	Benign	0.56	T
Sift4G	Benign	0.55	T
Polyphen		0.25	B
Vest4		0.18
MVP		0.61
MPC		1.1
ClinPred		0.061	T
GERP RS		1.6
PromoterAI		-0.046	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.4
Varity_R		0.12
gMVP		0.13
Mutation Taster		=96/4	polymorphism

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: rs573218643; hg19: chr1-206858672;