Variant chr22-50267141-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000330651.11(MAPK11):c.481G>A(p.Asp161Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000248 in 1,611,992 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 34)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

MAPK11
ENST00000330651.11 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.86

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MAPK11	NM_002751.7 linkuse as main transcript	c.481G>A	p.Asp161Asn	missense_variant	6/12	ENST00000330651.11	NP_002742.3
MAPK11	XM_047441447.1 linkuse as main transcript	c.157G>A	p.Asp53Asn	missense_variant	4/10		XP_047297403.1
MAPK11	NR_110887.2 linkuse as main transcript	n.569G>A		non_coding_transcript_exon_variant	6/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAPK11	ENST00000330651.11 linkuse as main transcript	c.481G>A	p.Asp161Asn	missense_variant	6/12	1	NM_002751.7	ENSP00000333685	P1	Q15759-1
MAPK11	ENST00000395764.5 linkuse as main transcript	c.481G>A	p.Asp161Asn	missense_variant, NMD_transcript_variant	6/13	1		ENSP00000379113		Q15759-1
MAPK11	ENST00000495277.1 linkuse as main transcript	n.563G>A		non_coding_transcript_exon_variant	4/4	4
MAPK11	ENST00000417877.1 linkuse as main transcript	c.485G>A	p.Gly162Glu	missense_variant, NMD_transcript_variant	6/12	5		ENSP00000409136

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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

AF:

0.00000137

AC:

AN:

1459768

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726168

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152224

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 19, 2024

The c.481G>A (p.D161N) alteration is located in exon 6 (coding exon 6) of the MAPK11 gene. This alteration results from a G to A substitution at nucleotide position 481, causing the aspartic acid (D) at amino acid position 161 to be replaced by an asparagine (N). 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

0.48

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.55

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.37

Eigen

Benign

-0.16

Eigen_PC

Benign

0.013

FATHMM_MKL

Benign

0.63

M_CAP

Benign

0.046

MetaRNN

Benign

0.23

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.040

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.92

PROVEAN

Uncertain

-4.3

REVEL

Benign

0.11

Sift

Benign

0.22

Sift4G

Benign

0.74

Polyphen

0.019

Vest4

0.34

MutPred

0.48

Loss of sheet (P = 0.302);

MVP

0.42

MPC

2.3

ClinPred

0.99

GERP RS

4.6

Varity_R

0.77

gMVP

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.39

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.39

Position offset: -3

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over