2-200871427-T-A

Variant names:

• chr2-200871427-T-A
• rs369410002
• NM_130906.3:c.454A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_130906.3(PPIL3):​c.454A>T​(p.Ile152Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,320 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I152V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PPIL3 NM_130906.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.56
• Publications: 4 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18166584).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_130906.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPIL3	NM_130906.3	MANE Select	c.454A>T	p.Ile152Leu	missense	Exon 7 of 7	NP_570981.1	Q9H2H8-1
	PPIL3	NM_032472.4		c.466A>T	p.Ile156Leu	missense	Exon 7 of 7	NP_115861.1	Q9H2H8-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPIL3	ENST00000392283.9	TSL:1 MANE Select	c.454A>T	p.Ile152Leu	missense	Exon 7 of 7	ENSP00000376107.4	Q9H2H8-1
	PPIL3	ENST00000286175.12	TSL:1	c.466A>T	p.Ile156Leu	missense	Exon 7 of 7	ENSP00000286175.8	Q9H2H8-2
	PPIL3	ENST00000465823.5	TSL:1	n.751A>T		non_coding_transcript_exon	Exon 6 of 6

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.0000119 AC: 3 AN: 251092 AF XY: 0.0000221

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1459320 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 726092

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33372

American (AMR) AF: 0.00 AC: 0 AN: 44632

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26102

East Asian (EAS) AF: 0.0000505 AC: 2 AN: 39634

South Asian (SAS) AF: 0.00 AC: 0 AN: 86142

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109964

Other (OTH) AF: 0.00 AC: 0 AN: 60304

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000203476), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0043	T
Eigen	Benign	-0.098
Eigen_PC	Benign	0.035
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		2.6
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.12
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.0080	D
Polyphen		0.0010	B
Vest4		0.33
MutPred		0.59		Gain of catalytic residue at I152 (P = 0.087)
MVP		0.31
MPC		0.23
ClinPred		0.53	D
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.77
gMVP		0.44
Mutation Taster		=77/23	polymorphism

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

Other links and lift over

dbSNP: rs369410002; hg19: chr2-201736150;