19-48873985-G-C

Variant names:

• chr19-48873985-G-C
• rs557806
• NM_014330.5:c.752G>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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: 𝑓 0.30 (10793 hom., cov: 32)
  • Exomes 𝑓: 0.16 (25017 hom.)
• Consequence: PPP1R15A NM_014330.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.198

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]

ACMG classification

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
PPP1R15A	NM_014330.5	c.752G>C	p.Arg251Pro	missense_variant	Exon 2 of 3	ENST00000200453.6	NP_055145.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP1R15A	ENST00000200453.6	c.752G>C	p.Arg251Pro	missense_variant	Exon 2 of 3	1	NM_014330.5	ENSP00000200453.4

Frequencies

GnomAD3 genomes AF: 0.297 AC: 45187 AN: 151916 Hom.: 10751 Cov.: 32

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

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

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

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

Other links and lift over

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