chr16-30121948-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_002746.3(MAPK3):c.229G>C(p.Glu77Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,858 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000041 ( 0 hom. )
Consequence
MAPK3
NM_002746.3 missense
NM_002746.3 missense
Scores
2
9
8
Clinical Significance
Conservation
PhyloP100: 7.91
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 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MAPK3 | NM_002746.3 | c.229G>C | p.Glu77Gln | missense_variant | 2/9 | ENST00000263025.9 | |
MAPK3 | NM_001040056.3 | c.229G>C | p.Glu77Gln | missense_variant | 2/7 | ||
MAPK3 | NM_001109891.2 | c.229G>C | p.Glu77Gln | missense_variant | 2/8 | ||
MAPK3 | XR_243293.2 | n.240G>C | non_coding_transcript_exon_variant | 2/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MAPK3 | ENST00000263025.9 | c.229G>C | p.Glu77Gln | missense_variant | 2/9 | 1 | NM_002746.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 genomes
?
Cov.:
31
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251320Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135856
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GnomAD4 exome AF: 0.00000410 AC: 6AN: 1461858Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 727228
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GnomAD4 genome ? Cov.: 31
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31
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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 | Apr 19, 2023 | The c.229G>C (p.E77Q) alteration is located in exon 2 (coding exon 2) of the MAPK3 gene. This alteration results from a G to C substitution at nucleotide position 229, causing the glutamic acid (E) at amino acid position 77 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Benign
T;.;T;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T;.;T
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D;D
MetaSVM
Uncertain
T
MutationAssessor
Benign
N;N;.;N;N
MutationTaster
Benign
D;D;D;D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;N;N;N;N
REVEL
Uncertain
Sift
Uncertain
D;D;D;D;D
Sift4G
Benign
T;T;T;T;T
Polyphen
P;D;.;D;P
Vest4
MutPred
Gain of MoRF binding (P = 0.0271);Gain of MoRF binding (P = 0.0271);.;Gain of MoRF binding (P = 0.0271);Gain of MoRF binding (P = 0.0271);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
Score
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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