rs769343391

Variant names:

• chr22-21684777-C-A
• NM_014337.4:c.578C>A

Your query was ambiguous. Multiple possible variants found:

• chr22-21684777-C-A
• chr22-21684777-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_014337.4(PPIL2):​c.578C>A​(p.Pro193Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,792 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PPIL2 NM_014337.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.65

Genes affected

PPIL2 (HGNC:9261): (peptidylprolyl isomerase like 2) This gene is a member of the cyclophilin family of peptidylprolyl isomerases. The cyclophilins are a highly conserved ubiquitous family, members of which play an important role in protein folding, immunosuppression by cyclosporin A, and infection of HIV-1 virions. This protein interacts with the proteinase inhibitor eglin c and is localized in the nucleus. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Dec 2015]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.794

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPIL2	NM_014337.4	c.578C>A	p.Pro193Gln	missense_variant	Exon 10 of 20	ENST00000398831.8	NP_055152.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPIL2	ENST00000398831.8	c.578C>A	p.Pro193Gln	missense_variant	Exon 10 of 20	1	NM_014337.4	ENSP00000381812.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461792 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727200

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.69
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.0
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.35	T;T;.;T
Eigen	Uncertain	0.67
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.92	.;.;D;D
M_CAP	Uncertain	0.15	D
MetaRNN	Pathogenic	0.79	D;D;D;D
MetaSVM	Benign	-0.73	T
MutationAssessor	Uncertain	2.6	M;M;M;M
PrimateAI	Uncertain	0.58	T
PROVEAN	Pathogenic	-6.3	D;D;.;D
REVEL	Benign	0.26
Sift	Uncertain	0.0020	D;D;.;D
Sift4G	Uncertain	0.0080	D;D;D;D
Polyphen		1.0	D;D;D;D
Vest4		0.72
MutPred		0.40		Loss of glycosylation at P193 (P = 0.0738);Loss of glycosylation at P193 (P = 0.0738);Loss of glycosylation at P193 (P = 0.0738);Loss of glycosylation at P193 (P = 0.0738);
MVP		0.60
ClinPred		0.99	D
GERP RS		3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.79
gMVP		0.64

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: chr22-22039066;