chr22-50266551-G-C

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_002751.7(MAPK11):c.671C>G(p.Pro224Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 1,365,620 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). 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: 0.000013 ( 0 hom. )

Consequence

MAPK11
NM_002751.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.21

Publications

1 publications found

Variant links:

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]

MAPK11 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAdExome4 at 18 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAPK11	NM_002751.7 link	c.671C>G	p.Pro224Arg	missense_variant	Exon 8 of 12	ENST00000330651.11	NP_002742.3	Q15759-1
MAPK11	XM_047441447.1 link	c.347C>G	p.Pro116Arg	missense_variant	Exon 6 of 10		XP_047297403.1
MAPK11	NR_110887.2 link	n.759C>G		non_coding_transcript_exon_variant	Exon 8 of 13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MAPK11	ENST00000330651.11 link	c.671C>G	p.Pro224Arg	missense_variant	Exon 8 of 12	1	NM_002751.7	ENSP00000333685.6	Q15759-1
MAPK11	ENST00000395764.5 link	n.671C>G		non_coding_transcript_exon_variant	Exon 8 of 13	1		ENSP00000379113.1	Q15759-1
MAPK11	ENST00000417877.1 link	n.*183C>G		non_coding_transcript_exon_variant	Exon 8 of 12	5		ENSP00000409136.1	F8WDP4
MAPK11	ENST00000417877.1 link	n.*183C>G		3_prime_UTR_variant	Exon 8 of 12	5		ENSP00000409136.1	F8WDP4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000337

AC:

AN:

177866

AF XY:

0.0000426

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000132

AC:

AN:

1365620

Hom.:

Cov.:

AF XY:

0.0000179

AC XY:

AN XY:

669046

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30256

American (AMR)

AF:

0.00

AC:

AN:

29476

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19958

East Asian (EAS)

AF:

0.00

AC:

AN:

38824

South Asian (SAS)

AF:

0.000241

AC:

AN:

70684

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48650

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5304

European-Non Finnish (NFE)

AF:

9.38e-7

AC:

AN:

1066338

Other (OTH)

AF:

0.00

AC:

AN:

56130

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000168

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 03, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.671C>G (p.P224R) alteration is located in exon 8 (coding exon 8) of the MAPK11 gene. This alteration results from a C to G substitution at nucleotide position 671, causing the proline (P) at amino acid position 224 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.47

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.13

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.42

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Uncertain

0.97

M_CAP

Uncertain

0.13

MetaRNN

Uncertain

0.68

MetaSVM

Benign

-0.57

MutationAssessor

Benign

1.3

PhyloP100

1.2

PrimateAI

Uncertain

0.78

PROVEAN

Pathogenic

-6.7

REVEL

Uncertain

0.37

Sift

Benign

0.078

Sift4G

Uncertain

0.057

Polyphen

0.95

Vest4

0.62

MutPred

0.61

Gain of catalytic residue at P224 (P = 0.0065);

MVP

0.83

MPC

0.83

ClinPred

0.72

GERP RS

4.3

Varity_R

0.77

gMVP

0.70

Mutation Taster

=51/49

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over