22-50266551-G-T

Variant names:

• chr22-50266551-G-T
• rs201406886
• NM_002751.7:c.671C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_002751.7(MAPK11):​c.671C>A​(p.Pro224Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. P224A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MAPK11 NM_002751.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.21
• Publications: 1 publications found

Genes affected

MAPK11 (HGNC:6873): (mitogen-activated protein kinase 11) This gene encodes a member of a family of protein kinases that are involved in the integration of biochemical signals for a wide variety of cellular processes, including cell proliferation, differentiation, transcriptional regulation, and development. The encoded protein can be activated by proinflammatory cytokines and environmental stresses through phosphorylation by mitogen activated protein kinase kinases (MKKs). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAPK11	NM_002751.7	c.671C>A	p.Pro224Gln	missense_variant	Exon 8 of 12	ENST00000330651.11	NP_002742.3
MAPK11	XM_047441447.1	c.347C>A	p.Pro116Gln	missense_variant	Exon 6 of 10		XP_047297403.1
MAPK11	NR_110887.2	n.759C>A		non_coding_transcript_exon_variant	Exon 8 of 13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAPK11	ENST00000330651.11	c.671C>A	p.Pro224Gln	missense_variant	Exon 8 of 12	1	NM_002751.7	ENSP00000333685.6
MAPK11	ENST00000395764.5	n.671C>A		non_coding_transcript_exon_variant	Exon 8 of 13	1		ENSP00000379113.1
MAPK11	ENST00000417877.1	n.*183C>A		non_coding_transcript_exon_variant	Exon 8 of 12	5		ENSP00000409136.1
MAPK11	ENST00000417877.1	n.*183C>A		3_prime_UTR_variant	Exon 8 of 12	5		ENSP00000409136.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1365620 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 669046

African (AFR) AF: 0.00 AC: 0 AN: 30256

American (AMR) AF: 0.00 AC: 0 AN: 29476

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19958

East Asian (EAS) AF: 0.00 AC: 0 AN: 38824

South Asian (SAS) AF: 0.00 AC: 0 AN: 70684

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48650

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5304

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1066338

Other (OTH) AF: 0.00 AC: 0 AN: 56130

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Uncertain	0.017	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.42	T
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.91	D
M_CAP	Uncertain	0.19	D
MetaRNN	Uncertain	0.67	D
MetaSVM	Benign	-0.53	T
MutationAssessor	Benign	1.6	L
PhyloP100		1.2
PrimateAI	Uncertain	0.73	T
PROVEAN	Pathogenic	-6.0	D
REVEL	Uncertain	0.36
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.033	D
Polyphen		0.98	D
Vest4		0.55
MutPred		0.57		Loss of ubiquitination at K220 (P = 0.0992);
MVP		0.82
MPC		0.76
ClinPred		0.98	D
GERP RS		4.3
Varity_R		0.83
gMVP		0.69
Mutation Taster		=49/51	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs201406886; hg19: chr22-50704980;