Genetic Variant PPRC1:p.Ser536Gly (chr10-102140114-A-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_015062.5(PPRC1):c.1606A>G(p.Ser536Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0138 in 1,614,220 control chromosomes in the GnomAD database, including 1,296 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.018 ( 135 hom., cov: 32)

Exomes 𝑓: 0.013 ( 1161 hom. )

Consequence

PPRC1
NM_015062.5 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.667

Publications

12 publications found

Variant links:

Genes affected

PPRC1 (HGNC:30025): (PPARG related coactivator 1) The protein encoded by this gene is similar to PPAR-gamma coactivator 1 (PPARGC1/PGC-1), a protein that can activate mitochondrial biogenesis in part through a direct interaction with nuclear respiratory factor 1 (NRF1). This protein has been shown to interact with NRF1. It is thought to be a functional relative of PPAR-gamma coactivator 1 that activates mitochondrial biogenesis through NRF1 in response to proliferative signals. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2013]

PPRC1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0015044808).

BP6

Variant 10-102140114-A-G is Benign according to our data. Variant chr10-102140114-A-G is described in ClinVar as [Benign]. Clinvar id is 3057089.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.162 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPRC1	NM_015062.5 link	c.1606A>G	p.Ser536Gly	missense_variant	Exon 5 of 14	ENST00000278070.7	NP_055877.3	Q5VV67-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPRC1	ENST00000278070.7 link	c.1606A>G	p.Ser536Gly	missense_variant	Exon 5 of 14	1	NM_015062.5	ENSP00000278070.2		Q5VV67-1
PPRC1	ENST00000413464.6 link	c.1606A>G	p.Ser536Gly	missense_variant	Exon 5 of 12	2		ENSP00000399743.2		E7EVG6

Frequencies

GnomAD3 genomes

AF:

0.0180

AC:

2739

AN:

152208

Hom.:

137

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0101

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0616

Gnomad ASJ

AF:

0.00548

Gnomad EAS

AF:

0.171

Gnomad SAS

AF:

0.0605

Gnomad FIN

AF:

0.000282

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00193

Gnomad OTH

AF:

0.0211

GnomAD2 exomes

AF:

0.0351

AC:

8824

AN:

251440

AF XY:

0.0331

show subpopulations

Gnomad AFR exome

AF:

0.00843

Gnomad AMR exome

AF:

0.0869

Gnomad ASJ exome

AF:

0.00446

Gnomad EAS exome

AF:

0.191

Gnomad FIN exome

AF:

0.000277

Gnomad NFE exome

AF:

0.00178

Gnomad OTH exome

AF:

0.0215

GnomAD4 exome

AF:

0.0134

AC:

19561

AN:

1461894

Hom.:

1161

Cov.:

AF XY:

0.0143

AC XY:

10402

AN XY:

727248

show subpopulations

African (AFR)

AF:

0.00962

AC:

322

AN:

33480

American (AMR)

AF:

0.0867

AC:

3877

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00532

AC:

139

AN:

26136

East Asian (EAS)

AF:

0.195

AC:

7751

AN:

39700

South Asian (SAS)

AF:

0.0566

AC:

4885

AN:

86258

European-Finnish (FIN)

AF:

0.000225

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.0276

AC:

159

AN:

5768

European-Non Finnish (NFE)

AF:

0.00132

AC:

1466

AN:

1112012

Other (OTH)

AF:

0.0157

AC:

950

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

1419

2838

4256

5675

7094

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0180

AC:

2740

AN:

152326

Hom.:

135

Cov.:

AF XY:

0.0207

AC XY:

1543

AN XY:

74490

show subpopulations

African (AFR)

AF:

0.0101

AC:

421

AN:

41580

American (AMR)

AF:

0.0616

AC:

943

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00548

AC:

AN:

3470

East Asian (EAS)

AF:

0.171

AC:

885

AN:

5178

South Asian (SAS)

AF:

0.0601

AC:

290

AN:

4826

European-Finnish (FIN)

AF:

0.000282

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00193

AC:

131

AN:

68018

Other (OTH)

AF:

0.0213

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

128

257

385

514

642

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0122

Hom.:

269

Bravo

AF:

0.0224

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.00885

AC:

ESP6500EA

AF:

0.00140

AC:

ExAC

AF:

0.0324

AC:

3938

Asia WGS

AF:

0.0860

AC:

299

AN:

3478

EpiCase

AF:

0.00354

EpiControl

AF:

0.00296

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PPRC1-related disorder

Benign:1

Apr 03, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as 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

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.56

CADD

Benign

0.060

(source)

DANN

Benign

0.83

DEOGEN2

Benign

0.016

T;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.097

LIST_S2

Benign

0.50

T;T

MetaRNN

Benign

0.0015

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.44

.;N

PhyloP100

-0.67

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.69

N;N

REVEL

Benign

0.041

Sift

Benign

0.56

T;T

Sift4G

Benign

0.27

T;T

Polyphen

0.0010

B;B

Vest4

0.067

MPC

0.077

ClinPred

0.0017

GERP RS

-6.0

Varity_R

0.035

gMVP

0.12

Mutation Taster

=100/0

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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chr10-102140114-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over