Genetic Variant NM_006247.4:c.492G>A (chr19-46375732-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

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

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -1.37

Variant links:

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]

PPP5C links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 link	c.492G>A	p.Ser164Ser	synonymous_variant	Exon 3 of 13	ENST00000012443.9	NP_006238.1	P53041A0A024R0Q7
PPP5C	NM_001204284.2 link	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 link	c.492G>A	p.Ser164Ser	synonymous_variant	Exon 3 of 13	1	NM_006247.4	ENSP00000012443.4		P53041

Frequencies

GnomAD3 genomes

AF:

0.221

AC:

33668

AN:

152102

Hom.:

4309

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.218

AC:

48879

AN:

223938

Hom.:

5409

AF XY:

0.221

AC XY:

26739

AN XY:

120856

show subpopulations

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 SAS exome

AF:

0.140

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.:

AF XY:

0.267

AC XY:

192353

AN XY:

719848

show subpopulations

Gnomad4 AFR exome

AF:

0.107

Gnomad4 AMR exome

AF:

0.151

Gnomad4 ASJ exome

AF:

0.259

Gnomad4 EAS exome

AF:

0.0511

Gnomad4 SAS exome

AF:

0.138

Gnomad4 FIN exome

AF:

0.252

Gnomad4 NFE exome

AF:

0.300

Gnomad4 OTH exome

AF:

0.254

GnomAD4 genome

AF:

0.221

AC:

33672

AN:

152220

Hom.:

4306

Cov.:

AF XY:

0.216

AC XY:

16097

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.117

Gnomad4 AMR

AF:

0.199

Gnomad4 ASJ

AF:

0.255

Gnomad4 EAS

AF:

0.0398

Gnomad4 SAS

AF:

0.126

Gnomad4 FIN

AF:

0.244

Gnomad4 NFE

AF:

0.303

Gnomad4 OTH

AF:

0.234

Alfa

AF:

0.274

Hom.:

1792

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

LINK: link

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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over