chr17-21304526-G-C
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate
The NM_145109.3(MAP2K3):āc.669G>Cā(p.Met223Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000546 in 1,612,914 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ).
Frequency
Genomes: š 0.00059 ( 0 hom., cov: 70)
Exomes š: 0.00054 ( 0 hom. )
Consequence
MAP2K3
NM_145109.3 missense
NM_145109.3 missense
Scores
3
16
Clinical Significance
Conservation
PhyloP100: 5.66
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 -2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.21132252).
BP6
Variant 17-21304526-G-C is Benign according to our data. Variant chr17-21304526-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 1109856.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.669G>C | p.Met223Ile | missense_variant | 8/12 | ENST00000342679.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MAP2K3 | ENST00000342679.9 | c.669G>C | p.Met223Ile | missense_variant | 8/12 | 1 | NM_145109.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000591 AC: 90AN: 152276Hom.: 0 Cov.: 70
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GnomAD3 exomes AF: 0.000326 AC: 82AN: 251332Hom.: 0 AF XY: 0.000405 AC XY: 55AN XY: 135840
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GnomAD4 exome AF: 0.000541 AC: 790AN: 1460520Hom.: 0 Cov.: 91 AF XY: 0.000534 AC XY: 388AN XY: 726608
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GnomAD4 genome AF: 0.000591 AC: 90AN: 152394Hom.: 0 Cov.: 70 AF XY: 0.000496 AC XY: 37AN XY: 74528
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 04, 2022 | - - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;.;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;.;.
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;.;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;.;.
REVEL
Benign
Sift
Benign
T;T;.;.
Sift4G
Benign
T;T;T;T
Polyphen
B;.;.;.
Vest4
MutPred
Loss of catalytic residue at V219 (P = 0.0153);.;.;.;
MVP
MPC
ClinPred
T
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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