dbSNP rs917948: PPP5C:p.Tyr44Tyr (chr19-46353758-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_006247.4(PPP5C):c.132C>T(p.Tyr44Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 1,613,882 control chromosomes in the GnomAD database, including 17,160 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.12 ( 1662 hom., cov: 33)

Exomes 𝑓: 0.12 ( 15498 hom. )

Consequence

PPP5C
NM_006247.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.975

Publications

21 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: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP7

Synonymous conserved (PhyloP=0.975 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.375 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP5C	NM_006247.4 link	c.132C>T	p.Tyr44Tyr	synonymous_variant	Exon 2 of 13	ENST00000012443.9	NP_006238.1	P53041A0A024R0Q7
PPP5C	NM_001204284.2 link	c.132C>T	p.Tyr44Tyr	synonymous_variant	Exon 2 of 12		NP_001191213.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PPP5C	ENST00000012443.9 link	c.132C>T	p.Tyr44Tyr	synonymous_variant	Exon 2 of 13	1	NM_006247.4	ENSP00000012443.4	P53041
PPP5C	ENST00000478046.5 link	n.126C>T		non_coding_transcript_exon_variant	Exon 2 of 14	1		ENSP00000434329.1	H0YDU8
PPP5C	ENST00000391919.1 link	c.-187C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 2 of 12	5		ENSP00000375786.1	A8MU39
PPP5C	ENST00000391919.1 link	c.-187C>T		5_prime_UTR_variant	Exon 2 of 12	5		ENSP00000375786.1	A8MU39

Frequencies

GnomAD3 genomes

AF:

0.120

AC:

18275

AN:

152128

Hom.:

1663

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0473

Gnomad AMI

AF:

0.118

Gnomad AMR

AF:

0.240

Gnomad ASJ

AF:

0.0441

Gnomad EAS

AF:

0.389

Gnomad SAS

AF:

0.103

Gnomad FIN

AF:

0.230

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.106

Gnomad OTH

AF:

0.101

GnomAD2 exomes

AF:

0.174

AC:

43551

AN:

250558

AF XY:

0.160

show subpopulations

Gnomad AFR exome

AF:

0.0465

Gnomad AMR exome

AF:

0.419

Gnomad ASJ exome

AF:

0.0438

Gnomad EAS exome

AF:

0.402

Gnomad FIN exome

AF:

0.217

Gnomad NFE exome

AF:

0.107

Gnomad OTH exome

AF:

0.138

GnomAD4 exome

AF:

0.124

AC:

180887

AN:

1461636

Hom.:

15498

Cov.:

AF XY:

0.121

AC XY:

87813

AN XY:

727134

show subpopulations

African (AFR)

AF:

0.0431

AC:

1443

AN:

33480

American (AMR)

AF:

0.395

AC:

17642

AN:

44674

Ashkenazi Jewish (ASJ)

AF:

0.0425

AC:

1112

AN:

26136

East Asian (EAS)

AF:

0.373

AC:

14814

AN:

39696

South Asian (SAS)

AF:

0.0944

AC:

8143

AN:

86238

European-Finnish (FIN)

AF:

0.210

AC:

11191

AN:

53344

Middle Eastern (MID)

AF:

0.0479

AC:

276

AN:

5768

European-Non Finnish (NFE)

AF:

0.107

AC:

118903

AN:

1111920

Other (OTH)

AF:

0.122

AC:

7363

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

9081

18163

27244

36326

45407

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4554

9108

13662

18216

22770

<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:

0.120

AC:

18296

AN:

152246

Hom.:

1662

Cov.:

AF XY:

0.128

AC XY:

9551

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.0475

AC:

1976

AN:

41564

American (AMR)

AF:

0.240

AC:

3671

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0441

AC:

153

AN:

3468

East Asian (EAS)

AF:

0.390

AC:

2013

AN:

5166

South Asian (SAS)

AF:

0.104

AC:

501

AN:

4828

European-Finnish (FIN)

AF:

0.230

AC:

2440

AN:

10598

Middle Eastern (MID)

AF:

0.0578

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.106

AC:

7202

AN:

68006

Other (OTH)

AF:

0.102

AC:

215

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

785

1570

2355

3140

3925

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

198

396

594

792

990

<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:

0.112

Hom.:

2741

Bravo

AF:

0.127

Asia WGS

AF:

0.240

AC:

834

AN:

3478

EpiCase

AF:

0.0955

EpiControl

AF:

0.0958

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Benign

0.66

PhyloP100

0.97

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=293/7

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over