10-79347730-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_005729.4(PPIF):​c.182G>T​(p.Arg61Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000785 in 1,273,532 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 7.9e-7 ( 0 hom. )

Consequence

PPIF
NM_005729.4 missense

Scores

12
4
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.34
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.909

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PPIFNM_005729.4 linkuse as main transcriptc.182G>T p.Arg61Leu missense_variant 1/6 ENST00000225174.8 NP_005720.1
PPIFXM_005269379.3 linkuse as main transcriptc.182G>T p.Arg61Leu missense_variant 1/6 XP_005269436.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PPIFENST00000225174.8 linkuse as main transcriptc.182G>T p.Arg61Leu missense_variant 1/61 NM_005729.4 ENSP00000225174 P1P30405-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
7.85e-7
AC:
1
AN:
1273532
Hom.:
0
Cov.:
31
AF XY:
0.00000160
AC XY:
1
AN XY:
625814
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.85e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

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 submitterclinical testingAmbry GeneticsJan 08, 2024The c.182G>T (p.R61L) alteration is located in exon 1 (coding exon 1) of the PPIF gene. This alteration results from a G to T substitution at nucleotide position 182, causing the arginine (R) at amino acid position 61 to be replaced by a leucine (L). 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
0.82
BayesDel_addAF
Pathogenic
0.32
D
BayesDel_noAF
Pathogenic
0.22
CADD
Pathogenic
33
DANN
Uncertain
1.0
DEOGEN2
Benign
0.34
T
Eigen
Pathogenic
0.70
Eigen_PC
Pathogenic
0.67
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Benign
0.78
T
M_CAP
Pathogenic
0.58
D
MetaRNN
Pathogenic
0.91
D
MetaSVM
Uncertain
-0.12
T
MutationAssessor
Pathogenic
4.0
H
MutationTaster
Benign
1.0
D;D
PrimateAI
Pathogenic
0.80
T
PROVEAN
Pathogenic
-5.7
D
REVEL
Uncertain
0.62
Sift
Pathogenic
0.0
D
Sift4G
Uncertain
0.010
D
Polyphen
0.71
P
Vest4
0.64
MutPred
0.77
Gain of catalytic residue at R61 (P = 0.0691);
MVP
0.83
MPC
2.1
ClinPred
1.0
D
GERP RS
4.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.95
gMVP
0.90

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-81107486; API