chr22-50267837-G-A
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The ENST00000330651.11(MAPK11):c.229C>T(p.His77Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 33)
Consequence
MAPK11
ENST00000330651.11 missense
ENST00000330651.11 missense
Scores
6
6
6
Clinical Significance
Conservation
PhyloP100: 7.87
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.772
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MAPK11 | NM_002751.7 | c.229C>T | p.His77Tyr | missense_variant | 2/12 | ENST00000330651.11 | NP_002742.3 | |
MAPK11 | XM_047441447.1 | c.-37C>T | 5_prime_UTR_variant | 1/10 | XP_047297403.1 | |||
MAPK11 | NR_110887.2 | n.317C>T | non_coding_transcript_exon_variant | 2/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MAPK11 | ENST00000330651.11 | c.229C>T | p.His77Tyr | missense_variant | 2/12 | 1 | NM_002751.7 | ENSP00000333685 | P1 | |
MAPK11 | ENST00000395764.5 | c.229C>T | p.His77Tyr | missense_variant, NMD_transcript_variant | 2/13 | 1 | ENSP00000379113 | |||
MAPK11 | ENST00000495277.1 | n.288C>T | non_coding_transcript_exon_variant | 2/4 | 4 | |||||
MAPK11 | ENST00000417877.1 | c.229C>T | p.His77Tyr | missense_variant, NMD_transcript_variant | 2/12 | 5 | ENSP00000409136 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD4 exome Cov.: 38
GnomAD4 exome
Cov.:
38
GnomAD4 genome Cov.: 33
GnomAD4 genome
Cov.:
33
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 26, 2021 | The c.229C>T (p.H77Y) alteration is located in exon 2 (coding exon 2) of the MAPK11 gene. This alteration results from a C to T substitution at nucleotide position 229, causing the histidine (H) at amino acid position 77 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D
MetaSVM
Benign
T
MutationAssessor
Benign
N
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D
REVEL
Uncertain
Sift
Pathogenic
D
Sift4G
Uncertain
T
Polyphen
D
Vest4
MutPred
Loss of methylation at K79 (P = 0.0763);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.