chr16-30123084-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM4
The NM_002746.3(MAPK3):c.126C>A(p.Tyr42Ter) variant causes a stop gained change involving the alteration of a non-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 (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 28)
Consequence
MAPK3
NM_002746.3 stop_gained
NM_002746.3 stop_gained
Scores
2
3
2
Clinical Significance
Conservation
PhyloP100: 2.21
Genes affected
MAPK3 (HGNC:6877): (mitogen-activated protein kinase 3) The protein encoded by this gene is a member of the MAP kinase family. MAP kinases, also known as extracellular signal-regulated kinases (ERKs), act in a signaling cascade that regulates various cellular processes such as proliferation, differentiation, and cell cycle progression in response to a variety of extracellular signals. This kinase is activated by upstream kinases, resulting in its translocation to the nucleus where it phosphorylates nuclear targets. Alternatively spliced transcript variants encoding different protein isoforms have been described. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PM4
?
Stoplost variant in NM_002746.3 Downstream stopcodon found after 241 codons.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MAPK3 | NM_002746.3 | c.126C>A | p.Tyr42Ter | stop_gained | 1/9 | ENST00000263025.9 | |
MAPK3 | NM_001040056.3 | c.126C>A | p.Tyr42Ter | stop_gained | 1/7 | ||
MAPK3 | NM_001109891.2 | c.126C>A | p.Tyr42Ter | stop_gained | 1/8 | ||
MAPK3 | XR_243293.2 | n.137C>A | non_coding_transcript_exon_variant | 1/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MAPK3 | ENST00000263025.9 | c.126C>A | p.Tyr42Ter | stop_gained | 1/9 | 1 | NM_002746.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 28
GnomAD3 genomes
?
Cov.:
28
GnomAD4 exome Cov.: 37
GnomAD4 exome
Cov.:
37
GnomAD4 genome ? Cov.: 28
GnomAD4 genome
?
Cov.:
28
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
MAPK3-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 29, 2023 | The MAPK3 c.126C>A variant is predicted to result in premature protein termination (p.Tyr42*). To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
D
MutationTaster
Benign
A;A;A;A;A;A
Vest4
GERP RS
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.