Genetic Variant PPP5C:p.Asp295Gly (chr19-46384889-A-G) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4BS2

The NM_006247.4(PPP5C):c.884A>G(p.Asp295Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000103 in 1,461,648 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

PPP5C
NM_006247.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.56

Publications

0 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:

PPP5C-AS1 (HGNC:58175):

PPP5C-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.2815867).

BS2

High AC in GnomAdExome4 at 15 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.884A>G	p.Asp295Gly	missense	Exon 7 of 13	NP_006238.1	P53041
	PPP5C	NM_001204284.2		c.818A>G	p.Asp273Gly	missense	Exon 6 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.884A>G	p.Asp295Gly	missense	Exon 7 of 13	ENSP00000012443.4	P53041
PPP5C	ENST00000478046.5	TSL:1	n.878A>G		non_coding_transcript_exon	Exon 7 of 14	ENSP00000434329.1	H0YDU8
PPP5C	ENST00000923870.1		c.917A>G	p.Asp306Gly	missense	Exon 7 of 13	ENSP00000593929.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000103

AC:

AN:

1461648

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

727142

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33472

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.00

AC:

AN:

86248

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000135

AC:

AN:

1111800

Other (OTH)

AF:

0.00

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.415

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

Cov.:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

0.092

BayesDel_addAF

Benign

-0.097

BayesDel_noAF

Benign

-0.38

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Pathogenic

0.80

Eigen

Benign

-0.11

Eigen_PC

Benign

0.029

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.015

MetaRNN

Benign

0.28

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

PhyloP100

5.6

PrimateAI

Uncertain

0.53

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.15

Sift

Benign

0.092

Sift4G

Benign

0.13

Polyphen

0.0010

Vest4

0.34

MutPred

0.44

Loss of stability (P = 0.0086)

MVP

0.55

MPC

0.90

ClinPred

0.75

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.30

gMVP

0.83

Mutation Taster

=49/51

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over