NM_014330.5:c.1962C>T

Variant names:

• chr19-48875910-C-T
• rs524
• NM_014330.5:c.1962C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_014330.5(PPP1R15A):​c.1962C>T​(p.Ala654Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 1,613,100 control chromosomes in the GnomAD database, including 72,966 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.35 (10432 hom., cov: 33)
  • Exomes 𝑓: 0.29 (62534 hom.)
• Consequence: PPP1R15A NM_014330.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.845
• Publications: 27 publications found

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

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP7: Synonymous conserved (PhyloP=0.845 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.524 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014330.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP1R15A	NM_014330.5	MANE Select	c.1962C>T	p.Ala654Ala	synonymous	Exon 3 of 3	NP_055145.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP1R15A	ENST00000200453.6	TSL:1 MANE Select	c.1962C>T	p.Ala654Ala	synonymous	Exon 3 of 3	ENSP00000200453.4
	PPP1R15A	ENST00000704027.1		c.2010C>T	p.Ala670Ala	synonymous	Exon 2 of 2	ENSP00000515637.1
	PPP1R15A	ENST00000704026.1		c.1677C>T	p.Ala559Ala	synonymous	Exon 4 of 4	ENSP00000515636.1

Frequencies

GnomAD3 genomes AF: 0.352 AC: 53441 AN: 152032 Hom.: 10418 Cov.: 33

Gnomad AFR AF: 0.529

Gnomad AMI AF: 0.348

Gnomad AMR AF: 0.302

Gnomad ASJ AF: 0.335

Gnomad EAS AF: 0.198

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.301

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.277

Gnomad OTH AF: 0.350

GnomAD2 exomes AF: 0.294 AC: 73739 AN: 250696 AF XY: 0.294

Gnomad AFR exome AF: 0.532

Gnomad AMR exome AF: 0.258

Gnomad ASJ exome AF: 0.318

Gnomad EAS exome AF: 0.179

Gnomad FIN exome AF: 0.313

Gnomad NFE exome AF: 0.275

Gnomad OTH exome AF: 0.307

GnomAD4 exome AF: 0.287 AC: 419609 AN: 1460950 Hom.: 62534 Cov.: 35 AF XY: 0.288 AC XY: 209280 AN XY: 726680

African (AFR) AF: 0.548 AC: 18344 AN: 33464

American (AMR) AF: 0.267 AC: 11902 AN: 44646

Ashkenazi Jewish (ASJ) AF: 0.325 AC: 8485 AN: 26094

East Asian (EAS) AF: 0.257 AC: 10181 AN: 39684

South Asian (SAS) AF: 0.330 AC: 28442 AN: 86206

European-Finnish (FIN) AF: 0.311 AC: 16628 AN: 53384

Middle Eastern (MID) AF: 0.316 AC: 1822 AN: 5762

European-Non Finnish (NFE) AF: 0.275 AC: 305592 AN: 1111348

Other (OTH) AF: 0.302 AC: 18213 AN: 60362

GnomAD4 genome AF: 0.352 AC: 53513 AN: 152150 Hom.: 10432 Cov.: 33 AF XY: 0.351 AC XY: 26116 AN XY: 74380

African (AFR) AF: 0.529 AC: 21969 AN: 41492

American (AMR) AF: 0.302 AC: 4610 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.335 AC: 1163 AN: 3472

East Asian (EAS) AF: 0.197 AC: 1023 AN: 5180

South Asian (SAS) AF: 0.328 AC: 1585 AN: 4826

European-Finnish (FIN) AF: 0.301 AC: 3189 AN: 10594

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.277 AC: 18839 AN: 67986

Other (OTH) AF: 0.348 AC: 735 AN: 2112

Alfa AF: 0.300 Hom.: 10972

Bravo AF: 0.356

Asia WGS AF: 0.275 AC: 954 AN: 3478

EpiCase AF: 0.281

EpiControl AF: 0.278

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	8.5
DANN	Benign	0.74
PhyloP100		0.84
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs524; hg19: chr19-49379167; COSMIC: COSV52338373;