rs1973505

chr12-110722198-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_002710.4(PPP1CC):c.819C>T(p.Cys273=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 1,613,756 control chromosomes in the GnomAD database, including 23,905 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 0.23 (6022 hom., cov: 32)
  • Exomes 𝑓: 0.14 (17883 hom.)
• Consequence: PPP1CC NM_002710.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.99

Genes affected

PPP1CC (HGNC:9283): (protein phosphatase 1 catalytic subunit gamma) The protein encoded by this gene belongs to the protein phosphatase family, PP1 subfamily. PP1 is an ubiquitous serine/threonine phosphatase that regulates many cellular processes, including cell division. It is expressed in mammalian cells as three closely related isoforms, alpha, beta/delta and gamma, which have distinct localization patterns. This gene encodes the gamma isozyme. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP7: Synonymous conserved (PhyloP=2.99 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.487 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPP1CC	NM_002710.4	c.819C>T	p.Cys273=	synonymous_variant	6/7	ENST00000335007.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP1CC	ENST00000335007.10	c.819C>T	p.Cys273=	synonymous_variant	6/7	1	NM_002710.4	P1

Frequencies

GnomAD3 genomes AF: 0.231 AC: 35142 AN: 151950 Hom.: 6005 Cov.: 32

Gnomad AFR AF: 0.492

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.0730

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.208

GnomAD3 exomes AF: 0.149 AC: 37559 AN: 251334 Hom.: 4065 AF XY: 0.147 AC XY: 19960 AN XY: 135844

Gnomad AFR exome AF: 0.498

Gnomad AMR exome AF: 0.0915

Gnomad ASJ exome AF: 0.176

Gnomad EAS exome AF: 0.0681

Gnomad SAS exome AF: 0.168

Gnomad FIN exome AF: 0.108

Gnomad NFE exome AF: 0.131

Gnomad OTH exome AF: 0.147

GnomAD4 exome AF: 0.142 AC: 208265 AN: 1461688 Hom.: 17883 Cov.: 32 AF XY: 0.142 AC XY: 103420 AN XY: 727136

Gnomad4 AFR exome AF: 0.511

Gnomad4 AMR exome AF: 0.0961

Gnomad4 ASJ exome AF: 0.172

Gnomad4 EAS exome AF: 0.0614

Gnomad4 SAS exome AF: 0.164

Gnomad4 FIN exome AF: 0.105

Gnomad4 NFE exome AF: 0.134

Gnomad4 OTH exome AF: 0.161

GnomAD4 genome AF: 0.231 AC: 35197 AN: 152068 Hom.: 6022 Cov.: 32 AF XY: 0.226 AC XY: 16816 AN XY: 74338

Gnomad4 AFR AF: 0.493

Gnomad4 AMR AF: 0.132

Gnomad4 ASJ AF: 0.173

Gnomad4 EAS AF: 0.0732

Gnomad4 SAS AF: 0.168

Gnomad4 FIN AF: 0.110

Gnomad4 NFE AF: 0.135

Gnomad4 OTH AF: 0.207

Alfa AF: 0.176 Hom.: 2311

Bravo AF: 0.246

Asia WGS AF: 0.150 AC: 524 AN: 3478

EpiCase AF: 0.142

EpiControl AF: 0.147

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
Cadd	Benign	10
Dann	Benign	0.63
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs1973505; hg19: chr12-111160003; COSMIC: COSV58583488;