NM_015062.5:c.61C>G

Variant names:

• chr10-102133129-C-G
• rs2068582543
• NM_015062.5:c.61C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015062.5(PPRC1):​c.61C>G​(p.Pro21Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PPRC1 NM_015062.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.63
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22189462).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPRC1	NM_015062.5	c.61C>G	p.Pro21Ala	missense_variant	Exon 1 of 14	ENST00000278070.7	NP_055877.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPRC1	ENST00000278070.7	c.61C>G	p.Pro21Ala	missense_variant	Exon 1 of 14	1	NM_015062.5	ENSP00000278070.2
PPRC1	ENST00000413464.6	c.61C>G	p.Pro21Ala	missense_variant	Exon 1 of 12	2		ENSP00000399743.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000936 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 17, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.61C>G (p.P21A) alteration is located in exon 1 (coding exon 1) of the PPRC1 gene. This alteration results from a C to G substitution at nucleotide position 61, causing the proline (P) at amino acid position 21 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.029	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.020	T;T
Eigen	Benign	0.15
Eigen_PC	Benign	0.099
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.85	D;D
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.22	T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	1.9	.;L
PhyloP100		1.6
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-1.3	N;N
REVEL	Benign	0.20
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;T
Polyphen		0.99	D;D
Vest4		0.40
MutPred		0.14		Loss of catalytic residue at P21 (P = 0.1129);Loss of catalytic residue at P21 (P = 0.1129);
MVP		0.22
MPC		2.5
ClinPred		0.94	D
GERP RS		5.2
PromoterAI		-0.017	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.30
gMVP		0.11
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2068582543; hg19: chr10-103892886;