19-48873985-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014330.5(PPP1R15A):​c.752G>C​(p.Arg251Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 1,613,804 control chromosomes in the GnomAD database, including 35,810 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: š‘“ 0.30 ( 10793 hom., cov: 32)
Exomes š‘“: 0.16 ( 25017 hom. )

Consequence

PPP1R15A
NM_014330.5 missense

Scores

18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.198
Variant links:
Genes affected
PPP1R15A (HGNC:14375): (protein phosphatase 1 regulatory subunit 15A) This gene is a member of a group of genes whose transcript levels are increased following stressful growth arrest conditions and treatment with DNA-damaging agents. The induction of this gene by ionizing radiation occurs in certain cell lines regardless of p53 status, and its protein response is correlated with apoptosis following ionizing radiation. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=2.8412487E-6).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.655 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PPP1R15ANM_014330.5 linkc.752G>C p.Arg251Pro missense_variant Exon 2 of 3 ENST00000200453.6 NP_055145.3 O75807-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PPP1R15AENST00000200453.6 linkc.752G>C p.Arg251Pro missense_variant Exon 2 of 3 1 NM_014330.5 ENSP00000200453.4 O75807-1

Frequencies

GnomAD3 genomes
AF:
0.297
AC:
45187
AN:
151916
Hom.:
10751
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.661
Gnomad AMI
AF:
0.0954
Gnomad AMR
AF:
0.241
Gnomad ASJ
AF:
0.198
Gnomad EAS
AF:
0.107
Gnomad SAS
AF:
0.286
Gnomad FIN
AF:
0.164
Gnomad MID
AF:
0.193
Gnomad NFE
AF:
0.134
Gnomad OTH
AF:
0.297
GnomAD3 exomes
AF:
0.202
AC:
50833
AN:
251148
Hom.:
7450
AF XY:
0.195
AC XY:
26426
AN XY:
135812
show subpopulations
Gnomad AFR exome
AF:
0.676
Gnomad AMR exome
AF:
0.208
Gnomad ASJ exome
AF:
0.192
Gnomad EAS exome
AF:
0.104
Gnomad SAS exome
AF:
0.264
Gnomad FIN exome
AF:
0.169
Gnomad NFE exome
AF:
0.140
Gnomad OTH exome
AF:
0.195
GnomAD4 exome
AF:
0.159
AC:
232924
AN:
1461770
Hom.:
25017
Cov.:
37
AF XY:
0.161
AC XY:
116847
AN XY:
727176
show subpopulations
Gnomad4 AFR exome
AF:
0.685
Gnomad4 AMR exome
AF:
0.217
Gnomad4 ASJ exome
AF:
0.198
Gnomad4 EAS exome
AF:
0.108
Gnomad4 SAS exome
AF:
0.262
Gnomad4 FIN exome
AF:
0.169
Gnomad4 NFE exome
AF:
0.132
Gnomad4 OTH exome
AF:
0.189
GnomAD4 genome
AF:
0.298
AC:
45291
AN:
152034
Hom.:
10793
Cov.:
32
AF XY:
0.297
AC XY:
22115
AN XY:
74340
show subpopulations
Gnomad4 AFR
AF:
0.662
Gnomad4 AMR
AF:
0.241
Gnomad4 ASJ
AF:
0.198
Gnomad4 EAS
AF:
0.107
Gnomad4 SAS
AF:
0.285
Gnomad4 FIN
AF:
0.164
Gnomad4 NFE
AF:
0.134
Gnomad4 OTH
AF:
0.294
Alfa
AF:
0.136
Hom.:
1382
Bravo
AF:
0.317
TwinsUK
AF:
0.136
AC:
504
ALSPAC
AF:
0.133
AC:
513
ESP6500AA
AF:
0.657
AC:
2894
ESP6500EA
AF:
0.133
AC:
1142
ExAC
AF:
0.210
AC:
25551
Asia WGS
AF:
0.237
AC:
821
AN:
3478
EpiCase
AF:
0.140
EpiControl
AF:
0.145

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.066
BayesDel_addAF
Benign
-0.85
T
BayesDel_noAF
Benign
-0.85
CADD
Benign
6.2
DANN
Benign
0.43
DEOGEN2
Benign
0.046
T
Eigen
Benign
-1.6
Eigen_PC
Benign
-1.5
FATHMM_MKL
Benign
0.0043
N
LIST_S2
Benign
0.18
T
MetaRNN
Benign
0.0000028
T
MetaSVM
Benign
-0.94
T
MutationAssessor
Benign
-1.8
N
PrimateAI
Benign
0.20
T
PROVEAN
Benign
0.48
N
REVEL
Benign
0.046
Sift
Benign
0.47
T
Sift4G
Benign
0.31
T
Polyphen
0.0
B
Vest4
0.029
MPC
0.12
ClinPred
0.0045
T
GERP RS
1.2
RBP_binding_hub_radar
0.92
RBP_regulation_power_radar
2.0
Varity_R
0.23
gMVP
0.093

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs557806; hg19: chr19-49377242; COSMIC: COSV52338692; COSMIC: COSV52338692; API