Variant 19-46347098-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 8P and 6B. PVS1BP6_ModerateBS2

The NM_006247.4(PPP5C):c.2T>C(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0013 in 1,600,796 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0015 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 15 hom. )

Consequence

PPP5C
NM_006247.4 start_lost

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.04

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 Uncertain_significance. Variant got 2 ACMG points.

PVS1

Start lost variant, no new inframe start found.

BP6

Variant 19-46347098-T-C is Benign according to our data. Variant chr19-46347098-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3053594.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 224 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPP5C	NM_006247.4 linkuse as main transcript	c.2T>C	p.Met1?	start_lost	1/13	ENST00000012443.9
PPP5C	NM_001204284.2 linkuse as main transcript	c.2T>C	p.Met1?	start_lost	1/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
PPP5C	ENST00000012443.9 linkuse as main transcript	c.2T>C	p.Met1?	start_lost	1/13	1	NM_006247.4	P1
PPP5C	ENST00000478046.5 linkuse as main transcript			upstream_gene_variant		1
PPP5C	ENST00000391919.1 linkuse as main transcript			upstream_gene_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00148

AC:

225

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000851

Gnomad ASJ

AF:

0.0444

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000676

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00222

AC:

499

AN:

224840

Hom.:

AF XY:

0.00215

AC XY:

262

AN XY:

122074

show subpopulations

Gnomad AFR exome

AF:

0.000222

Gnomad AMR exome

AF:

0.000804

Gnomad ASJ exome

AF:

0.0378

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000281

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000731

Gnomad OTH exome

AF:

0.00579

GnomAD4 exome

AF:

0.00128

AC:

1859

AN:

1448504

Hom.:

Cov.:

AF XY:

0.00132

AC XY:

953

AN XY:

719434

show subpopulations

Gnomad4 AFR exome

AF:

0.000422

Gnomad4 AMR exome

AF:

0.000885

Gnomad4 ASJ exome

AF:

0.0407

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000344

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000414

Gnomad4 OTH exome

AF:

0.00397

GnomAD4 genome

AF:

0.00147

AC:

224

AN:

152292

Hom.:

Cov.:

AF XY:

0.00130

AC XY:

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.000850

Gnomad4 ASJ

AF:

0.0444

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000676

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00281

Hom.:

Bravo

AF:

0.00164

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00187

AC:

ExAC

AF:

0.00151

AC:

182

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

PPP5C-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 14, 2020

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_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.25

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.18

FATHMM_MKL

Benign

0.51

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.082

MetaRNN

Benign

0.011

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

PROVEAN

Benign

-0.21

REVEL

Benign

0.22

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.025

Polyphen

0.0060

Vest4

0.62

MVP

0.56

ClinPred

0.15

GERP RS

3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.90

gMVP

0.56

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