NM_032833.5:c.25C>T
Variant names:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_032833.5(PPP1R15B):c.25C>T(p.Arg9Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R9G) has been classified as Uncertain significance.
Frequency
Genomes: not found (cov: 33)
Consequence
PPP1R15B
NM_032833.5 missense
NM_032833.5 missense
Scores
2
6
8
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 2.18
Genes affected
PPP1R15B (HGNC:14951): (protein phosphatase 1 regulatory subunit 15B) This gene encodes a protein phosphatase I-interacting protein that promotes the dephosphorylation of eukaryotic translation initiation factor 2A to regulate translation under conditions of cellular stress. The transcribed messenger RNA contains two upstream open reading frames (ORFs) that repress translation of the main protein coding ORF under normal conditions, while the protein coding ORF is expressed at high levels in response to stress. Continual translation of the mRNA under conditions of eukaryotic translation initiation factor 2A inactivation is thought to create a feedback loop for reactivation of the gene during recovery from stress. In addition, it has been shown that this protein plays a role in membrane traffic that is independent of translation and that it is required for exocytosis from erythroleukemia cells. Allelic variants of this gene are associated with microcephaly, short stature, and impaired glucose metabolism. [provided by RefSeq, Feb 2016]
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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 |
|---|---|---|---|---|---|---|---|---|
| PPP1R15B | NM_032833.5 | c.25C>T | p.Arg9Trp | missense_variant | Exon 1 of 2 | ENST00000367188.5 | NP_116222.4 | |
| PPP1R15B | XM_005245551.6 | c.25C>T | p.Arg9Trp | missense_variant | Exon 1 of 3 | XP_005245608.2 | ||
| PPP1R15B | XM_047432518.1 | c.25C>T | p.Arg9Trp | missense_variant | Exon 1 of 3 | XP_047288474.1 |
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD3 exomes AF: 0.00000401 AC: 1AN: 249130Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135480
GnomAD3 exomes
AF:
AC:
1
AN:
249130
Hom.:
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AC XY:
0
AN XY:
135480
Gnomad AFR exome
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GnomAD4 exome Cov.: 33
GnomAD4 exome
Cov.:
33
GnomAD4 genome
GnomAD4 genome
Cov.:
33
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Benign
N
M_CAP
Uncertain
D
MetaRNN
Uncertain
D
MetaSVM
Benign
T
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Pathogenic
D
Sift4G
Pathogenic
D
Vest4
MutPred
Loss of methylation at R9 (P = 0.0268);
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
gMVP
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