chr19-46375732-G-A

Variant names:

• chr19-46375732-G-A
• rs4239538
• NM_006247.4:c.492G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_006247.4(PPP5C):​c.492G>A​(p.Ser164Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 1,601,346 control chromosomes in the GnomAD database, including 55,404 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.22 (4306 hom., cov: 33)
  • Exomes 𝑓: 0.27 (51098 hom.)
• Consequence: PPP5C NM_006247.4 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -1.37

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 19-46375732-G-A is Benign according to our data. Variant chr19-46375732-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3059137.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.299 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP5C	NM_006247.4	c.492G>A	p.Ser164Ser	synonymous_variant	Exon 3 of 13	ENST00000012443.9	NP_006238.1
PPP5C	NM_001204284.2	c.492G>A	p.Ser164Ser	synonymous_variant	Exon 3 of 12		NP_001191213.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP5C	ENST00000012443.9	c.492G>A	p.Ser164Ser	synonymous_variant	Exon 3 of 13	1	NM_006247.4	ENSP00000012443.4

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33668 AN: 152102 Hom.: 4309 Cov.: 33

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.327

Gnomad AMR AF: 0.199

Gnomad ASJ AF: 0.255

Gnomad EAS AF: 0.0397

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.244

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.303

Gnomad OTH AF: 0.234

GnomAD2 exomes AF: 0.218 AC: 48879 AN: 223938 AF XY: 0.221

Gnomad AFR exome AF: 0.112

Gnomad AMR exome AF: 0.144

Gnomad ASJ exome AF: 0.256

Gnomad EAS exome AF: 0.0381

Gnomad FIN exome AF: 0.245

Gnomad NFE exome AF: 0.298

Gnomad OTH exome AF: 0.250

GnomAD4 exome AF: 0.270 AC: 391502 AN: 1449126 Hom.: 51098 Cov.: 34 AF XY: 0.267 AC XY: 192353 AN XY: 719848

Gnomad4 AFR exome AF: 0.107 AC: 3562 AN: 33182

Gnomad4 AMR exome AF: 0.151 AC: 6496 AN: 43058

Gnomad4 ASJ exome AF: 0.259 AC: 6707 AN: 25862

Gnomad4 EAS exome AF: 0.0511 AC: 1998 AN: 39118

Gnomad4 SAS exome AF: 0.138 AC: 11714 AN: 84614

Gnomad4 FIN exome AF: 0.252 AC: 13238 AN: 52450

Gnomad4 NFE exome AF: 0.300 AC: 331142 AN: 1105220

Gnomad4 Remaining exome AF: 0.254 AC: 15206 AN: 59890

GnomAD4 genome AF: 0.221 AC: 33672 AN: 152220 Hom.: 4306 Cov.: 33 AF XY: 0.216 AC XY: 16097 AN XY: 74420

Gnomad4 AFR AF: 0.117 AC: 0.117457 AN: 0.117457

Gnomad4 AMR AF: 0.199 AC: 0.198836 AN: 0.198836

Gnomad4 ASJ AF: 0.255 AC: 0.255472 AN: 0.255472

Gnomad4 EAS AF: 0.0398 AC: 0.039753 AN: 0.039753

Gnomad4 SAS AF: 0.126 AC: 0.125932 AN: 0.125932

Gnomad4 FIN AF: 0.244 AC: 0.244103 AN: 0.244103

Gnomad4 NFE AF: 0.303 AC: 0.302955 AN: 0.302955

Gnomad4 OTH AF: 0.234 AC: 0.23368 AN: 0.23368

Alfa AF: 0.272 Hom.: 1801

Bravo AF: 0.216

Asia WGS AF: 0.0980 AC: 342 AN: 3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

PPP5C-related disorder Benign:1

Jun 17, 2023

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.34
DANN	Benign	0.55
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
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

Publications

LitVar

Other links and lift over

dbSNP: rs4239538; hg19: chr19-46878989; COSMIC: COSV50145188;