rs55776345

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002754.5(MAPK13):​c.122C>A​(p.Ser41*) variant causes a stop gained, splice region change. The variant allele was found at a frequency of 0.000000685 in 1,459,596 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 1/1 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

MAPK13
NM_002754.5 stop_gained, splice_region

Scores

2
4
1

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.89
Variant links:
Genes affected
MAPK13 (HGNC:6875): (mitogen-activated protein kinase 13) This gene encodes a member of the mitogen-activated protein (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. The encoded protein is a p38 MAP kinase and is activated by proinflammatory cytokines and cellular stress. Substrates of the encoded protein include the transcription factor ATF2 and the microtubule dynamics regulator stathmin. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Jul 2012]

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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 rank MANE Protein UniProt
MAPK13NM_002754.5 linkc.122C>A p.Ser41* stop_gained, splice_region_variant Exon 2 of 12 ENST00000211287.9 NP_002745.1 O15264-1A0A024RD04
MAPK13NR_072996.2 linkn.192C>A splice_region_variant, non_coding_transcript_exon_variant Exon 2 of 10

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MAPK13ENST00000211287.9 linkc.122C>A p.Ser41* stop_gained, splice_region_variant Exon 2 of 12 1 NM_002754.5 ENSP00000211287.4 O15264-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1459596
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
726044
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.55
D
BayesDel_noAF
Pathogenic
0.56
CADD
Pathogenic
47
DANN
Uncertain
0.99
Eigen
Uncertain
0.61
Eigen_PC
Uncertain
0.42
FATHMM_MKL
Uncertain
0.91
D
Vest4
0.90
GERP RS
3.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.3

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.75
Details are displayed if max score is > 0.2
DS_AG_spliceai
0.75
Position offset: 2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-36099050; API