6-36073707-A-G
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_139012.3(MAPK14):c.434A>G(p.Asp145Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000992 in 1,612,838 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000010 ( 1 hom. )
Consequence
MAPK14
NM_139012.3 missense
NM_139012.3 missense
Scores
1
2
12
Clinical Significance
Conservation
PhyloP100: 2.19
Genes affected
MAPK14 (HGNC:6876): (mitogen-activated protein kinase 14) The protein encoded by this gene is a member of the MAP kinase family. MAP kinases act as an integration point for multiple biochemical signals, and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation and development. This kinase is activated by various environmental stresses and proinflammatory cytokines. The activation requires its phosphorylation by MAP kinase kinases (MKKs), or its autophosphorylation triggered by the interaction of MAP3K7IP1/TAB1 protein with this kinase. The substrates of this kinase include transcription regulator ATF2, MEF2C, and MAX, cell cycle regulator CDC25B, and tumor suppressor p53, which suggest the roles of this kinase in stress related transcription and cell cycle regulation, as well as in genotoxic stress response. Four alternatively spliced transcript variants of this gene encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.047435135).
BS2
?
High AC in GnomAdExome at 16 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MAPK14 | NM_139012.3 | c.434A>G | p.Asp145Gly | missense_variant | 5/12 | ENST00000229794.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MAPK14 | ENST00000229794.9 | c.434A>G | p.Asp145Gly | missense_variant | 5/12 | 1 | NM_139012.3 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152244Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000639 AC: 16AN: 250308Hom.: 0 AF XY: 0.0000665 AC XY: 9AN XY: 135386
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GnomAD4 exome AF: 0.0000103 AC: 15AN: 1460594Hom.: 1 Cov.: 30 AF XY: 0.00000963 AC XY: 7AN XY: 726682
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GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152244Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74376
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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 10, 2023 | The c.434A>G (p.D145G) alteration is located in exon 5 (coding exon 5) of the MAPK14 gene. This alteration results from a A to G substitution at nucleotide position 434, causing the aspartic acid (D) at amino acid position 145 to be replaced by a glycine (G). 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
Benign
Cadd
Benign
Dann
Benign
DEOGEN2
Benign
T;.;T;T;.;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D;D;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D
PrimateAI
Pathogenic
D
Sift4G
Benign
T;T;T;T;T;T
Polyphen
0.0
.;B;B;.;B;.
Vest4
MutPred
Loss of stability (P = 0.0131);Loss of stability (P = 0.0131);Loss of stability (P = 0.0131);.;Loss of stability (P = 0.0131);.;
MVP
MPC
1.3
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