22-50265328-C-A

Variant names:

• chr22-50265328-C-A
• rs150537389
• NM_002751.7:c.1008G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002751.7(MAPK11):​c.1008G>T​(p.Glu336Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MAPK11 NM_002751.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.923
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38833714).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002751.7. 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
	MAPK11	NM_002751.7	MANE Select	c.1008G>T	p.Glu336Asp	missense	Exon 11 of 12	NP_002742.3
	MAPK11	NR_110887.2		n.1096G>T		non_coding_transcript_exon	Exon 11 of 13

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPK11	ENST00000330651.11	TSL:1 MANE Select	c.1008G>T	p.Glu336Asp	missense	Exon 11 of 12	ENSP00000333685.6	Q15759-1
	MAPK11	ENST00000395764.5	TSL:1	n.1008G>T		non_coding_transcript_exon	Exon 11 of 13	ENSP00000379113.1	Q15759-1
	MAPK11	ENST00000880442.1		c.969G>T	p.Glu323Asp	missense	Exon 11 of 12	ENSP00000550501.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.0023	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.45	T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.69	D
M_CAP	Benign	0.054	D
MetaRNN	Benign	0.39	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	1.6	L
PhyloP100		0.92
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-2.2	N
REVEL	Uncertain	0.30
Sift	Benign	0.052	T
Sift4G	Benign	0.18	T
Polyphen		0.0020	B
Vest4		0.63
MutPred		0.28		Loss of ubiquitination at K338 (P = 0.2113)
MVP		0.68
MPC		0.70
ClinPred		0.82	D
GERP RS		3.3
Varity_R		0.67
gMVP		0.38
Mutation Taster		=42/58	disease causing

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: rs150537389; hg19: chr22-50703757;