dbSNP rs760601651: PPP5C:p.Thr9Ser (chr19-46347122-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006247.4(PPP5C):c.26C>G(p.Thr9Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000275 in 1,452,216 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

PPP5C
NM_006247.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.84

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09919575).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP5C	NM_006247.4 link	c.26C>G	p.Thr9Ser	missense_variant	Exon 1 of 13	ENST00000012443.9	NP_006238.1	P53041A0A024R0Q7
PPP5C	NM_001204284.2 link	c.26C>G	p.Thr9Ser	missense_variant	Exon 1 of 12		NP_001191213.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PPP5C	ENST00000012443.9 link	c.26C>G	p.Thr9Ser	missense_variant	Exon 1 of 13	1	NM_006247.4	ENSP00000012443.4	P53041
PPP5C	ENST00000478046.5 link	n.20C>G		non_coding_transcript_exon_variant	Exon 1 of 14	1		ENSP00000434329.1	H0YDU8
PPP5C	ENST00000391919 link	c.-293C>G		5_prime_UTR_variant	Exon 1 of 12	5		ENSP00000375786.1	A8MU39

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000871

AC:

AN:

229498

Hom.:

AF XY:

0.00000802

AC XY:

AN XY:

124612

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000195

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000275

AC:

AN:

1452216

Hom.:

Cov.:

AF XY:

0.00000277

AC XY:

AN XY:

721544

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000361

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000468

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.68

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.25

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.23

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.67

M_CAP

Benign

0.014

MetaRNN

Benign

0.099

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.34

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-0.090

REVEL

Benign

0.078

Sift

Benign

0.030

Sift4G

Benign

0.15

Polyphen

0.0

Vest4

0.19

MutPred

0.080

Gain of glycosylation at T9 (P = 0.0738);

MVP

0.35

MPC

0.61

ClinPred

0.22

GERP RS

3.2

RBP_binding_hub_radar

1.0

RBP_regulation_power_radar

2.8

Varity_R

0.18

gMVP

0.24

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over