Variant rs7562391 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_130906.3(PPIL3):c.438T>G(p.Asp146Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 1,606,606 control chromosomes in the GnomAD database, including 16,263 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.19 ( 3711 hom., cov: 31)

Exomes 𝑓: 0.12 ( 12552 hom. )

Consequence

PPIL3
NM_130906.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.345

Variant links:

Genes affected

PPIL3 (HGNC:9262): (peptidylprolyl isomerase like 3) This gene encodes a member of the cyclophilin family. Cyclophilins catalyze the cis-trans isomerization of peptidylprolyl imide bonds in oligopeptides. They have been proposed to act either as catalysts or as molecular chaperones in protein-folding events. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2008]

PPIL3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0023481846).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.365 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPIL3	NM_130906.3 linkuse as main transcript	c.438T>G	p.Asp146Glu	missense_variant	7/7	ENST00000392283.9	NP_570981.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPIL3	ENST00000392283.9 linkuse as main transcript	c.438T>G	p.Asp146Glu	missense_variant	7/7	1	NM_130906.3	ENSP00000376107	P1	Q9H2H8-1

Frequencies

GnomAD3 genomes

AF:

0.187

AC:

28490

AN:

152036

Hom.:

3703

Cov.:

show subpopulations

Gnomad AFR

AF:

0.370

Gnomad AMI

AF:

0.118

Gnomad AMR

AF:

0.136

Gnomad ASJ

AF:

0.149

Gnomad EAS

AF:

0.00770

Gnomad SAS

AF:

0.0506

Gnomad FIN

AF:

0.101

Gnomad MID

AF:

0.114

Gnomad NFE

AF:

0.128

Gnomad OTH

AF:

0.178

GnomAD3 exomes

AF:

0.118

AC:

29616

AN:

251224

Hom.:

2600

AF XY:

0.113

AC XY:

15278

AN XY:

135786

show subpopulations

Gnomad AFR exome

AF:

0.386

Gnomad AMR exome

AF:

0.0814

Gnomad ASJ exome

AF:

0.134

Gnomad EAS exome

AF:

0.00457

Gnomad SAS exome

AF:

0.0564

Gnomad FIN exome

AF:

0.108

Gnomad NFE exome

AF:

0.126

Gnomad OTH exome

AF:

0.120

GnomAD4 exome

AF:

0.122

AC:

177630

AN:

1454452

Hom.:

12552

Cov.:

AF XY:

0.120

AC XY:

86721

AN XY:

723952

show subpopulations

Gnomad4 AFR exome

AF:

0.380

Gnomad4 AMR exome

AF:

0.0874

Gnomad4 ASJ exome

AF:

0.138

Gnomad4 EAS exome

AF:

0.00252

Gnomad4 SAS exome

AF:

0.0571

Gnomad4 FIN exome

AF:

0.107

Gnomad4 NFE exome

AF:

0.125

Gnomad4 OTH exome

AF:

0.129

GnomAD4 genome

AF:

0.188

AC:

28536

AN:

152154

Hom.:

3711

Cov.:

AF XY:

0.183

AC XY:

13591

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.370

Gnomad4 AMR

AF:

0.136

Gnomad4 ASJ

AF:

0.149

Gnomad4 EAS

AF:

0.00771

Gnomad4 SAS

AF:

0.0505

Gnomad4 FIN

AF:

0.101

Gnomad4 NFE

AF:

0.128

Gnomad4 OTH

AF:

0.177

Alfa

AF:

0.135

Hom.:

4249

Bravo

AF:

0.200

TwinsUK

AF:

0.127

AC:

471

ALSPAC

AF:

0.128

AC:

492

ESP6500AA

AF:

0.372

AC:

1639

ESP6500EA

AF:

0.128

AC:

1100

ExAC

AF:

0.123

AC:

14905

Asia WGS

AF:

0.0630

AC:

219

AN:

3478

EpiCase

AF:

0.122

EpiControl

AF:

0.134

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.85

DEOGEN2

Benign

0.00062

.;T;T;T;.

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.37

FATHMM_MKL

Uncertain

0.76

LIST_S2

Uncertain

0.89

.;D;D;D;D

MetaRNN

Benign

0.0023

T;T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.48

.;N;.;.;.

MutationTaster

Benign

0.000054

P;P;P;P

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-0.33

N;N;N;N;N

REVEL

Benign

0.13

Sift

Benign

1.0

T;T;T;T;T

Sift4G

Benign

0.69

T;T;T;T;T

Polyphen

0.0010

B;B;.;.;B

Vest4

0.035

MutPred

0.16

.;Loss of ubiquitination at K150 (P = 0.1423);.;.;.;

MPC

0.22

ClinPred

0.0019

GERP RS

1.1

Varity_R

0.11

gMVP

0.28

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over