chr12-111886029-T-C
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_003668.4(MAPKAPK5):āc.962T>Cā(p.Met321Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000075 in 1,613,618 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 (ā ).
Frequency
Genomes: š 0.00044 ( 0 hom., cov: 32)
Exomes š: 0.000037 ( 0 hom. )
Consequence
MAPKAPK5
NM_003668.4 missense
NM_003668.4 missense
Scores
2
3
14
Clinical Significance
Conservation
PhyloP100: 7.60
Genes affected
MAPKAPK5 (HGNC:6889): (MAPK activated protein kinase 5) The protein encoded by this gene is a tumor suppressor and member of the serine/threonine kinase family. In response to cellular stress and proinflammatory cytokines, this kinase is activated through its phosphorylation by MAP kinases including MAPK1/ERK, MAPK14/p38-alpha, and MAPK11/p38-beta. The encoded protein is found in the nucleus but translocates to the cytoplasm upon phosphorylation and activation. This kinase phosphorylates heat shock protein HSP27 at its physiologically relevant sites. Two alternately spliced transcript variants of this gene encoding distinct isoforms have been reported. [provided by RefSeq, Nov 2012]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.11043239).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MAPKAPK5 | NM_003668.4 | c.962T>C | p.Met321Thr | missense_variant | 10/14 | ENST00000550735.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MAPKAPK5 | ENST00000550735.7 | c.962T>C | p.Met321Thr | missense_variant | 10/14 | 1 | NM_003668.4 | P4 |
Frequencies
GnomAD3 genomes AF: 0.000441 AC: 67AN: 151924Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000189 AC: 47AN: 249260Hom.: 0 AF XY: 0.000133 AC XY: 18AN XY: 135228
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GnomAD4 exome AF: 0.0000369 AC: 54AN: 1461694Hom.: 0 Cov.: 31 AF XY: 0.0000261 AC XY: 19AN XY: 727132
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GnomAD4 genome AF: 0.000441 AC: 67AN: 151924Hom.: 0 Cov.: 32 AF XY: 0.000687 AC XY: 51AN XY: 74202
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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 | Oct 27, 2023 | The c.962T>C (p.M321T) alteration is located in exon 10 (coding exon 10) of the MAPKAPK5 gene. This alteration results from a T to C substitution at nucleotide position 962, causing the methionine (M) at amino acid position 321 to be replaced by a threonine (T). 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
Benign
T
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Benign
DEOGEN2
Benign
.;T;T
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N;.
MutationTaster
Benign
D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;N;.
REVEL
Benign
Sift
Benign
T;T;.
Sift4G
Benign
T;T;T
Polyphen
P;B;.
Vest4
MutPred
Loss of stability (P = 0.0131);Loss of stability (P = 0.0131);.;
MVP
MPC
0.64
ClinPred
T
GERP RS
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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