rs917948

chr19-46353758-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_006247.4(PPP5C):c.132C>T(p.Tyr44=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 1,613,882 control chromosomes in the GnomAD database, including 17,160 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 0.12 (1662 hom., cov: 33)
  • Exomes 𝑓: 0.12 (15498 hom.)
• Consequence: PPP5C NM_006247.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.975

Genes affected

PPP5C (HGNC:9322): (protein phosphatase 5 catalytic subunit) This gene encodes a serine/threonine phosphatase which is a member of the protein phosphatase catalytic subunit family. Proteins in this family participate in pathways regulated by reversible phosphorylation at serine and threonine residues; many of these pathways are involved in the regulation of cell growth and differentiation. The product of this gene has been shown to participate in signaling pathways in response to hormones or cellular stress, and elevated levels of this protein may be associated with breast cancer development. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2011]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP7: Synonymous conserved (PhyloP=0.975 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.375 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPP5C	NM_006247.4	c.132C>T	p.Tyr44=	synonymous_variant	2/13	ENST00000012443.9
PPP5C	NM_001204284.2	c.132C>T	p.Tyr44=	synonymous_variant	2/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP5C	ENST00000012443.9	c.132C>T	p.Tyr44=	synonymous_variant	2/13	1	NM_006247.4	P1
PPP5C	ENST00000478046.5	c.129C>T	p.Tyr43=	synonymous_variant, NMD_transcript_variant	2/14	1
PPP5C	ENST00000391919.1	c.-187C>T		5_prime_UTR_variant	2/12	5

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18275 AN: 152128 Hom.: 1663 Cov.: 33

Gnomad AFR AF: 0.0473

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.240

Gnomad ASJ AF: 0.0441

Gnomad EAS AF: 0.389

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.230

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.101

GnomAD3 exomes AF: 0.174 AC: 43551 AN: 250558 Hom.: 6354 AF XY: 0.160 AC XY: 21681 AN XY: 135528

Gnomad AFR exome AF: 0.0465

Gnomad AMR exome AF: 0.419

Gnomad ASJ exome AF: 0.0438

Gnomad EAS exome AF: 0.402

Gnomad SAS exome AF: 0.0932

Gnomad FIN exome AF: 0.217

Gnomad NFE exome AF: 0.107

Gnomad OTH exome AF: 0.138

GnomAD4 exome AF: 0.124 AC: 180887 AN: 1461636 Hom.: 15498 Cov.: 32 AF XY: 0.121 AC XY: 87813 AN XY: 727134

Gnomad4 AFR exome AF: 0.0431

Gnomad4 AMR exome AF: 0.395

Gnomad4 ASJ exome AF: 0.0425

Gnomad4 EAS exome AF: 0.373

Gnomad4 SAS exome AF: 0.0944

Gnomad4 FIN exome AF: 0.210

Gnomad4 NFE exome AF: 0.107

Gnomad4 OTH exome AF: 0.122

GnomAD4 genome AF: 0.120 AC: 18296 AN: 152246 Hom.: 1662 Cov.: 33 AF XY: 0.128 AC XY: 9551 AN XY: 74440

Gnomad4 AFR AF: 0.0475

Gnomad4 AMR AF: 0.240

Gnomad4 ASJ AF: 0.0441

Gnomad4 EAS AF: 0.390

Gnomad4 SAS AF: 0.104

Gnomad4 FIN AF: 0.230

Gnomad4 NFE AF: 0.106

Gnomad4 OTH AF: 0.102

Alfa AF: 0.108 Hom.: 1906

Bravo AF: 0.127

Asia WGS AF: 0.240 AC: 834 AN: 3478

EpiCase AF: 0.0955

EpiControl AF: 0.0958

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
Cadd	Benign	13
Dann	Benign	0.66
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: rs917948; hg19: chr19-46857015; COSMIC: COSV50140272;