2-200877033-T-C

Variant names:

• chr2-200877033-T-C
• rs754163849
• NM_130906.3:c.245A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_130906.3(PPIL3):​c.245A>G​(p.Asn82Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 1,441,556 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000013 (0 hom.)
• Consequence: PPIL3 NM_130906.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.127
• Publications: 1 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07469693).
• BP6: Variant 2-200877033-T-C is Benign according to our data. Variant chr2-200877033-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3782287.Status of the report is criteria_provided_single_submitter, 1 stars.

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.245A>G	p.Asn82Ser	missense	Exon 6 of 7	NP_570981.1	Q9H2H8-1
	PPIL3	NM_032472.4		c.257A>G	p.Asn86Ser	missense	Exon 6 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.245A>G	p.Asn82Ser	missense	Exon 6 of 7	ENSP00000376107.4	Q9H2H8-1
	PPIL3	ENST00000286175.12	TSL:1	c.257A>G	p.Asn86Ser	missense	Exon 6 of 7	ENSP00000286175.8	Q9H2H8-2
	PPIL3	ENST00000465823.5	TSL:1	n.542A>G		non_coding_transcript_exon	Exon 5 of 6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000797 AC: 2 AN: 251068 AF XY: 0.00000737

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000132 AC: 19 AN: 1441556 Hom.: 0 Cov.: 26 AF XY: 0.0000111 AC XY: 8 AN XY: 718502

African (AFR) AF: 0.0000304 AC: 1 AN: 32924

American (AMR) AF: 0.00 AC: 0 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26006

East Asian (EAS) AF: 0.00 AC: 0 AN: 39562

South Asian (SAS) AF: 0.00 AC: 0 AN: 85804

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5728

European-Non Finnish (NFE) AF: 0.0000165 AC: 18 AN: 1093724

Other (OTH) AF: 0.00 AC: 0 AN: 59718

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.057
BayesDel_addAF	Benign	-0.084	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	0.27
DANN	Benign	0.72
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.23	T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.075	T
MetaSVM	Benign	-1.1	T
PhyloP100		0.13
PROVEAN	Benign	-0.26	N
REVEL	Benign	0.17
Sift	Pathogenic	0.0	D
MutPred		0.34		Gain of helix (P = 0.027)
MVP		0.19
ClinPred		0.068	T
GERP RS		-7.7
Varity_R		0.22
Mutation Taster		=79/21	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs754163849; hg19: chr2-201741756;