chr17-21304522-C-T
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP3BP4_StrongBP6_Moderate
The NM_145109.3(MAP2K3):c.665C>T(p.Thr222Met) variant causes a missense change involving the alteration of a conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.30 ( 0 hom., cov: 69)
Exomes 𝑓: 0.26 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
MAP2K3
NM_145109.3 missense
NM_145109.3 missense
Scores
10
4
4
Clinical Significance
Conservation
PhyloP100: 7.81
Genes affected
MAP2K3 (HGNC:6843): (mitogen-activated protein kinase kinase 3) The protein encoded by this gene is a dual specificity protein kinase that belongs to the MAP kinase kinase family. This kinase is activated by mitogenic and environmental stress, and participates in the MAP kinase-mediated signaling cascade. It phosphorylates and thus activates MAPK14/p38-MAPK. This kinase can be activated by insulin, and is necessary for the expression of glucose transporter. Expression of RAS oncogene is found to result in the accumulation of the active form of this kinase, which thus leads to the constitutive activation of MAPK14, and confers oncogenic transformation of primary cells. The inhibition of this kinase is involved in the pathogenesis of Yersina pseudotuberculosis. Multiple alternatively spliced transcript variants that encode distinct isoforms have been reported for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
PP3
?
Multiple lines of computational evidence support a deleterious effect 9: AlphaMissense, BayesDel_addAF, BayesDel_noAF, Cadd, Dann, Eigen, phyloP100way_vertebrate, PrimateAI, PROVEAN [when max_spliceai, FATHMM_MKL, MetaRNN, MutationTaster was below the threshold]
BP4
?
Computational evidence support a benign effect (MetaRNN=0.005416125).
BP6
?
Variant 17-21304522-C-T is Benign according to our data. Variant chr17-21304522-C-T is described in ClinVar as [Benign]. Clinvar id is 768851.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MAP2K3 | NM_145109.3 | c.665C>T | p.Thr222Met | missense_variant | 8/12 | ENST00000342679.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MAP2K3 | ENST00000342679.9 | c.665C>T | p.Thr222Met | missense_variant | 8/12 | 1 | NM_145109.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00 AC: 41211AN: 137676Hom.: 0 Cov.: 69 FAILED QC
GnomAD3 genomes
?
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137676
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69
FAILED QC
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GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.261 AC: 322360AN: 1233950Hom.: 0 Cov.: 95 AF XY: 0.261 AC XY: 161078AN XY: 616044
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Data not reliable, filtered out with message: InbreedingCoeff
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GnomAD4 genome ? Data not reliable, filtered out with message: InbreedingCoeff AF: 0.299 AC: 41251AN: 137790Hom.: 0 Cov.: 69 AF XY: 0.293 AC XY: 19761AN XY: 67442
GnomAD4 genome
?
Data not reliable, filtered out with message: InbreedingCoeff
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2019 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Pathogenic
DEOGEN2
Benign
T;.;.;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D;D;.;.
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;.;.
MutationTaster
Benign
D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D;.;.
REVEL
Uncertain
Sift
Pathogenic
D;D;.;.
Sift4G
Uncertain
D;D;D;D
Polyphen
D;.;.;.
Vest4
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at