chr16-30117001-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_002746.3(MAPK3):c.910C>T(p.Leu304Phe) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000276 in 1,448,810 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000028 ( 0 hom. )
Consequence
MAPK3
NM_002746.3 missense, splice_region
NM_002746.3 missense, splice_region
Scores
2
12
5
Clinical Significance
Conservation
PhyloP100: 5.02
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 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MAPK3 | NM_002746.3 | c.910C>T | p.Leu304Phe | missense_variant, splice_region_variant | 7/9 | ENST00000263025.9 | |
MAPK3 | NM_001040056.3 | c.910C>T | p.Leu304Phe | missense_variant, splice_region_variant | 7/7 | ||
MAPK3 | NM_001109891.2 | c.778C>T | p.Leu260Phe | missense_variant, splice_region_variant | 6/8 | ||
MAPK3 | XR_243293.2 | n.921C>T | splice_region_variant, non_coding_transcript_exon_variant | 7/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MAPK3 | ENST00000263025.9 | c.910C>T | p.Leu304Phe | missense_variant, splice_region_variant | 7/9 | 1 | NM_002746.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 genomes
?
Cov.:
31
GnomAD3 exomes AF: 0.00000414 AC: 1AN: 241386Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 129964
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GnomAD4 exome AF: 0.00000276 AC: 4AN: 1448810Hom.: 0 Cov.: 32 AF XY: 0.00000139 AC XY: 1AN XY: 719012
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GnomAD4 genome ? Cov.: 31
GnomAD4 genome
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Cov.:
31
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 07, 2022 | The c.910C>T (p.L304F) alteration is located in exon 7 (coding exon 7) of the MAPK3 gene. This alteration results from a C to T substitution at nucleotide position 910, causing the leucine (L) at amino acid position 304 to be replaced by a phenylalanine (F). 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
Pathogenic
D;D;D;D;.;D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D;D;D;D
MetaSVM
Uncertain
T
MutationAssessor
Benign
L;.;.;.;.;.;L
MutationTaster
Benign
D;D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D;D;D;D;D
REVEL
Uncertain
Sift
Uncertain
D;D;D;D;D;D;D
Sift4G
Uncertain
D;D;D;D;D;D;D
Polyphen
D;.;P;.;P;.;D
Vest4
MutPred
Loss of ubiquitination at K302 (P = 0.0615);.;.;.;.;.;Loss of ubiquitination at K302 (P = 0.0615);
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
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Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at