chr10-102140114-A-G

Variant names:

• chr10-102140114-A-G
• rs17114388
• NM_015062.5:c.1606A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The ENST00000278070.7(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 ENST00000278070.7 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.667
• Publications: 12 publications found

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

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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000278070.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPRC1	NM_015062.5	MANE Select	c.1606A>G	p.Ser536Gly	missense	Exon 5 of 14	NP_055877.3
	PPRC1	NM_001288728.2		c.1246A>G	p.Ser416Gly	missense	Exon 5 of 14	NP_001275657.1
	PPRC1	NM_001288727.2		c.1606A>G	p.Ser536Gly	missense	Exon 5 of 12	NP_001275656.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPRC1	ENST00000278070.7	TSL:1 MANE Select	c.1606A>G	p.Ser536Gly	missense	Exon 5 of 14	ENSP00000278070.2
	PPRC1	ENST00000413464.6	TSL:2	c.1606A>G	p.Ser536Gly	missense	Exon 5 of 12	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

GnomAD2 exomes AF: 0.0351 AC: 8824 AN: 251440 AF XY: 0.0331

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

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: 12 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

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

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: 19 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: 3 AN: 10626

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00193 AC: 131 AN: 68018

Other (OTH) AF: 0.0213 AC: 45 AN: 2112

Alfa AF: 0.0122 Hom.: 269

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

ClinVar submissions as Germline

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	PPRC1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.097	N
LIST_S2	Benign	0.50	T
MetaRNN	Benign	0.0015	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.44	N
PhyloP100		-0.67
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.69	N
REVEL	Benign	0.041
Sift	Benign	0.56	T
Sift4G	Benign	0.27	T
Polyphen		0.0010	B
Vest4		0.067
MPC		0.077
ClinPred		0.0017	T
GERP RS		-6.0
Varity_R		0.035
gMVP		0.12
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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