rs17114388

Positions:

• chr10-102140114-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

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. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.018 (135 hom., cov: 32)
  • Exomes 𝑓: 0.013 (1161 hom.)
• Consequence: PPRC1 NM_015062.5 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.667

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
PPRC1	NM_015062.5	c.1606A>G	p.Ser536Gly	missense_variant	5/14	ENST00000278070.7	NP_055877.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPRC1	ENST00000278070.7	c.1606A>G	p.Ser536Gly	missense_variant	5/14	1	NM_015062.5	ENSP00000278070.2
PPRC1	ENST00000413464.6	c.1606A>G	p.Ser536Gly	missense_variant	5/12	2		ENSP00000399743.2

Frequencies

GnomAD3 genomes AF: 0.0180 AC: 2739 AN: 152208 Hom.: 137 Cov.: 32

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

GnomAD3 exomes AF: 0.0351 AC: 8824 AN: 251440 Hom.: 529 AF XY: 0.0331 AC XY: 4503 AN XY: 135900

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 SAS exome AF: 0.0585

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.: 33 AF XY: 0.0143 AC XY: 10402 AN XY: 727248

Gnomad4 AFR exome AF: 0.00962

Gnomad4 AMR exome AF: 0.0867

Gnomad4 ASJ exome AF: 0.00532

Gnomad4 EAS exome AF: 0.195

Gnomad4 SAS exome AF: 0.0566

Gnomad4 FIN exome AF: 0.000225

Gnomad4 NFE exome AF: 0.00132

Gnomad4 OTH exome AF: 0.0157

GnomAD4 genome AF: 0.0180 AC: 2740 AN: 152326 Hom.: 135 Cov.: 32 AF XY: 0.0207 AC XY: 1543 AN XY: 74490

Gnomad4 AFR AF: 0.0101

Gnomad4 AMR AF: 0.0616

Gnomad4 ASJ AF: 0.00548

Gnomad4 EAS AF: 0.171

Gnomad4 SAS AF: 0.0601

Gnomad4 FIN AF: 0.000282

Gnomad4 NFE AF: 0.00193

Gnomad4 OTH AF: 0.0213

Alfa AF: 0.0111 Hom.: 185

Bravo AF: 0.0224

TwinsUK AF: 0.00162 AC: 6

ALSPAC AF: 0.00104 AC: 4

ESP6500AA AF: 0.00885 AC: 39

ESP6500EA AF: 0.00140 AC: 12

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

Submissions by phenotype

PPRC1-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 03, 2019

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	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	0.060
DANN	Benign	0.83
DEOGEN2	Benign	0.016	T;T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.097	N
LIST_S2	Benign	0.50	T;T
MetaRNN	Benign	0.0015	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.44	.;N
PrimateAI	Benign	0.32	T
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	T
GERP RS		-6.0
Varity_R		0.035
gMVP		0.12

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

LitVar

Other links and lift over

dbSNP: rs17114388; hg19: chr10-103899871; COSMIC: COSV53384058; COSMIC: COSV53384058;