Variant 22-50265396-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_002751.7(MAPK11):c.940C>T(p.Pro314Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000011 in 1,460,800 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

MAPK11
NM_002751.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.04

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:

MAPK11 (HGNC:):

MAPK11 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAdExome4 at 16 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAPK11	NM_002751.7 linkuse as main transcript	c.940C>T	p.Pro314Ser	missense_variant	11/12	ENST00000330651.11	NP_002742.3	Q15759-1
MAPK11	XM_047441447.1 linkuse as main transcript	c.616C>T	p.Pro206Ser	missense_variant	9/10		XP_047297403.1
MAPK11	NR_110887.2 linkuse as main transcript	n.1028C>T		non_coding_transcript_exon_variant	11/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MAPK11	ENST00000330651.11 linkuse as main transcript	c.940C>T	p.Pro314Ser	missense_variant	11/12	1	NM_002751.7	ENSP00000333685.6	Q15759-1
MAPK11	ENST00000395764.5 linkuse as main transcript	n.940C>T		non_coding_transcript_exon_variant	11/13	1		ENSP00000379113.1	Q15759-1
MAPK11	ENST00000417877.1 linkuse as main transcript	n.*452C>T		non_coding_transcript_exon_variant	11/12	5		ENSP00000409136.1	F8WDP4
MAPK11	ENST00000417877.1 linkuse as main transcript	n.*452C>T		3_prime_UTR_variant	11/12	5		ENSP00000409136.1	F8WDP4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

250732

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135788

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000265

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000110

AC:

AN:

1460800

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

726708

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.0000135

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000178

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

Jul 13, 2022

The c.940C>T (p.P314S) alteration is located in exon 11 (coding exon 11) of the MAPK11 gene. This alteration results from a C to T substitution at nucleotide position 940, causing the proline (P) at amino acid position 314 to be replaced by a serine (S). 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

Benign

0.17

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.41

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.79

Eigen

Benign

-0.061

Eigen_PC

Benign

-0.19

FATHMM_MKL

Benign

0.72

M_CAP

Benign

0.021

MetaRNN

Uncertain

0.51

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.0

PrimateAI

Uncertain

0.65

PROVEAN

Pathogenic

-5.7

REVEL

Benign

0.17

Sift

Benign

0.060

Sift4G

Uncertain

0.040

Polyphen

0.87

Vest4

0.44

MutPred

0.36

Gain of phosphorylation at P314 (P = 0.023);

MVP

0.53

MPC

0.25

ClinPred

0.90

GERP RS

1.9

Varity_R

0.46

gMVP

0.50

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

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