Variant 10-79347601-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005729.4(PPIF):c.53G>C(p.Arg18Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000197 in 1,428,814 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00020 ( 0 hom. )

Consequence

PPIF
NM_005729.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.29

Variant links:

Genes affected

PPIF (HGNC:9259): (peptidylprolyl isomerase F) The protein encoded by this gene is a member of the peptidyl-prolyl cis-trans isomerase (PPIase) family. PPIases catalyze the cis-trans isomerization of proline imidic peptide bonds in oligopeptides and accelerate the folding of proteins. This protein is part of the mitochondrial permeability transition pore in the inner mitochondrial membrane. Activation of this pore is thought to be involved in the induction of apoptotic and necrotic cell death. [provided by RefSeq, Jul 2008]

PPIF links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08329585).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPIF	NM_005729.4 linkuse as main transcript	c.53G>C	p.Arg18Pro	missense_variant	1/6	ENST00000225174.8	NP_005720.1
PPIF	XM_005269379.3 linkuse as main transcript	c.53G>C	p.Arg18Pro	missense_variant	1/6		XP_005269436.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPIF	ENST00000225174.8 linkuse as main transcript	c.53G>C	p.Arg18Pro	missense_variant	1/6	1	NM_005729.4	ENSP00000225174	P1	P30405-1
PPIF	ENST00000492149.1 linkuse as main transcript	n.102G>C		non_coding_transcript_exon_variant	1/3	2
PPIF	ENST00000498681.5 linkuse as main transcript	n.133G>C		non_coding_transcript_exon_variant	1/4	2
PPIF	ENST00000472580.6 linkuse as main transcript	c.53G>C	p.Arg18Pro	missense_variant, NMD_transcript_variant	1/6	5		ENSP00000473548

Frequencies

GnomAD3 genomes

AF:

0.000158

AC:

AN:

152028

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000590

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.000123

AC:

AN:

64888

Hom.:

AF XY:

0.000160

AC XY:

AN XY:

37510

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000836

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000730

Gnomad FIN exome

AF:

0.000140

Gnomad NFE exome

AF:

0.000225

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000202

AC:

258

AN:

1276680

Hom.:

Cov.:

AF XY:

0.000205

AC XY:

129

AN XY:

627878

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000900

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000766

Gnomad4 FIN exome

AF:

0.000184

Gnomad4 NFE exome

AF:

0.000225

Gnomad4 OTH exome

AF:

0.000172

GnomAD4 genome

AF:

0.000151

AC:

AN:

152134

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.000589

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.000948

Alfa

AF:

0.000285

Hom.:

Bravo

AF:

0.000295

ExAC

AF:

0.000128

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 30, 2022

The c.53G>C (p.R18P) alteration is located in exon 1 (coding exon 1) of the PPIF gene. This alteration results from a G to C substitution at nucleotide position 53, causing the arginine (R) at amino acid position 18 to be replaced by a proline (P). 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

-0.31

BayesDel_noAF

Benign

-0.39

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.23

Eigen

Benign

-0.75

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.74

M_CAP

Benign

0.080

MetaRNN

Benign

0.083

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

MutationTaster

Benign

1.0

N;N

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-1.1

REVEL

Benign

0.20

Sift

Benign

0.037

Sift4G

Benign

0.35

Polyphen

0.0

Vest4

0.47

MutPred

0.24

Loss of MoRF binding (P = 0.0026);

MVP

0.59

MPC

1.6

ClinPred

0.15

GERP RS

1.7

Varity_R

0.41

gMVP

0.56

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over