chr2-200871443-A-C

Position:

• chr2-200871443-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000392283.9(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 ENST00000392283.9 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.345

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]

ACMG classification

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	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	c.438T>G	p.Asp146Glu	missense_variant	7/7	1	NM_130906.3	ENSP00000376107	P1

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28490 AN: 152036 Hom.: 3703 Cov.: 31

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

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.: 30 AF XY: 0.120 AC XY: 86721 AN XY: 723952

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.: 31 AF XY: 0.183 AC XY: 13591 AN XY: 74414

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	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	15
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	D
LIST_S2	Uncertain	0.89	.;D;D;D;D
MetaRNN	Benign	0.0023	T;T;T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.48	.;N;.;.;.
MutationTaster	Benign	0.000054	P;P;P;P
PrimateAI	Uncertain	0.62	T
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	T
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

Other links and lift over

dbSNP: rs7562391; hg19: chr2-201736166; COSMIC: COSV53768841;