Genetic Variant NM_006247.4:c.41C>G (chr19-46347137-C-G) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_006247.4(PPP5C):c.41C>G(p.Pro14Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000685 in 1,605,038 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000063 ( 0 hom. )

Consequence

PPP5C
NM_006247.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.25

Publications

4 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.088517964).

BS2

High AC in GnomAd4 at 19 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006247.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP5C	NM_006247.4	MANE Select	c.41C>G	p.Pro14Arg	missense	Exon 1 of 13	NP_006238.1	P53041
	PPP5C	NM_001204284.2		c.41C>G	p.Pro14Arg	missense	Exon 1 of 12	NP_001191213.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PPP5C	ENST00000012443.9	TSL:1 MANE Select	c.41C>G	p.Pro14Arg	missense	Exon 1 of 13	ENSP00000012443.4	P53041
PPP5C	ENST00000478046.5	TSL:1	n.35C>G		non_coding_transcript_exon	Exon 1 of 14	ENSP00000434329.1	H0YDU8
PPP5C	ENST00000923870.1		c.41C>G	p.Pro14Arg	missense	Exon 1 of 13	ENSP00000593929.1

Frequencies

GnomAD3 genomes

AF:

0.000125

AC:

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000109

AC:

AN:

229254

AF XY:

0.000121

show subpopulations

Gnomad AFR exome

AF:

0.000215

Gnomad AMR exome

AF:

0.0000920

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000232

Gnomad FIN exome

AF:

0.0000521

Gnomad NFE exome

AF:

0.000117

Gnomad OTH exome

AF:

0.000178

GnomAD4 exome

AF:

0.0000626

AC:

AN:

1452728

Hom.:

Cov.:

AF XY:

0.0000665

AC XY:

AN XY:

721840

show subpopulations

African (AFR)

AF:

0.000180

AC:

AN:

33346

American (AMR)

AF:

0.000207

AC:

AN:

43474

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25896

East Asian (EAS)

AF:

0.0000508

AC:

AN:

39362

South Asian (SAS)

AF:

0.0000590

AC:

AN:

84770

European-Finnish (FIN)

AF:

0.0000192

AC:

AN:

52058

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5740

European-Non Finnish (NFE)

AF:

0.0000541

AC:

AN:

1108104

Other (OTH)

AF:

0.000133

AC:

AN:

59978

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000125

AC:

AN:

152310

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

74466

show subpopulations

African (AFR)

AF:

0.000120

AC:

AN:

41576

American (AMR)

AF:

0.000327

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000132

AC:

AN:

68016

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00000439

Hom.:

Bravo

AF:

0.000295

ExAC

AF:

0.0000829

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.29

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.38

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.71

M_CAP

Benign

0.022

MetaRNN

Benign

0.089

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

PhyloP100

1.2

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-0.72

REVEL

Benign

0.082

Sift

Uncertain

0.0070

Sift4G

Benign

0.26

Polyphen

0.0020

Vest4

0.26

MutPred

0.21

Loss of catalytic residue at P14 (P = 0.011)

MVP

0.24

MPC

0.74

ClinPred

0.058

GERP RS

2.2

PromoterAI

0.0015

Neutral

(source)

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.1

Varity_R

0.089

gMVP

0.47

Mutation Taster

=96/4

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over