10-102138722-T-C

Position:

• chr10-102138722-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015062.5(PPRC1):​c.446T>C​(p.Ile149Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PPRC1 NM_015062.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.85

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPRC1	NM_015062.5	c.446T>C	p.Ile149Thr	missense_variant	3/14	ENST00000278070.7	NP_055877.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPRC1	ENST00000278070.7	c.446T>C	p.Ile149Thr	missense_variant	3/14	1	NM_015062.5	ENSP00000278070.2
PPRC1	ENST00000413464.6	c.446T>C	p.Ile149Thr	missense_variant	3/12	2		ENSP00000399743.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 05, 2024

The c.446T>C (p.I149T) alteration is located in exon 3 (coding exon 3) of the PPRC1 gene. This alteration results from a T to C substitution at nucleotide position 446, causing the isoleucine (I) at amino acid position 149 to be replaced by a threonine (T). 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	Pathogenic	0.91
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.046	T;T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.79	T;T
M_CAP	Benign	0.026	D
MetaRNN	Uncertain	0.45	T;T
MetaSVM	Benign	-0.67	T
MutationAssessor	Benign	1.9	.;L
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-1.7	N;N
REVEL	Benign	0.26
Sift	Pathogenic	0.0	D;D
Sift4G	Uncertain	0.013	D;T
Polyphen		1.0	D;D
Vest4		0.57
MutPred		0.22		Gain of glycosylation at I149 (P = 0.0086);Gain of glycosylation at I149 (P = 0.0086);
MVP		0.41
MPC		0.51
ClinPred		0.90	D
GERP RS		5.0
Varity_R		0.26
gMVP		0.30

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: rs2068816604; hg19: chr10-103898479;