Genetic Variant PPIG:p.Thr54Thr (chr2-169606064-T-A) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_004792.3(PPIG):c.162T>A(p.Thr54Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0112 in 1,612,600 control chromosomes in the GnomAD database, including 121 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0071 ( 6 hom., cov: 31)

Exomes 𝑓: 0.012 ( 115 hom. )

Consequence

PPIG
NM_004792.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0240

Variant links:

Genes affected

PPIG (HGNC:14650): (peptidylprolyl isomerase G) Enables cyclosporin A binding activity and peptidyl-prolyl cis-trans isomerase activity. Involved in protein peptidyl-prolyl isomerization. Located in cytosol and nuclear speck. [provided by Alliance of Genome Resources, Apr 2022]

PPIG links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 2-169606064-T-A is Benign according to our data. Variant chr2-169606064-T-A is described in ClinVar as [Benign]. Clinvar id is 773127.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.024 with no splicing effect.

BS2

High AC in GnomAd4 at 1079 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPIG	NM_004792.3 link	c.162T>A	p.Thr54Thr	synonymous_variant	Exon 5 of 14	ENST00000260970.8	NP_004783.2	Q13427-1
PPIG	XM_005246966.3 link	c.162T>A	p.Thr54Thr	synonymous_variant	Exon 5 of 14		XP_005247023.1	Q13427-1
PPIG	XM_005246967.2 link	c.162T>A	p.Thr54Thr	synonymous_variant	Exon 5 of 14		XP_005247024.1	Q13427-1
PPIG	XM_017005302.3 link	c.162T>A	p.Thr54Thr	synonymous_variant	Exon 5 of 12		XP_016860791.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPIG	ENST00000260970.8 link	c.162T>A	p.Thr54Thr	synonymous_variant	Exon 5 of 14	1	NM_004792.3	ENSP00000260970.3		Q13427-1

Frequencies

GnomAD3 genomes

AF:

0.00709

AC:

1079

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00270

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00399

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00518

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0121

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00733

AC:

1839

AN:

251048

Hom.:

AF XY:

0.00724

AC XY:

982

AN XY:

135716

show subpopulations

Gnomad AFR exome

AF:

0.00252

Gnomad AMR exome

AF:

0.00359

Gnomad ASJ exome

AF:

0.00516

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000883

Gnomad FIN exome

AF:

0.00504

Gnomad NFE exome

AF:

0.0127

Gnomad OTH exome

AF:

0.00703

GnomAD4 exome

AF:

0.0116

AC:

16971

AN:

1460302

Hom.:

115

Cov.:

AF XY:

0.0113

AC XY:

8175

AN XY:

726512

show subpopulations

Gnomad4 AFR exome

AF:

0.00275

Gnomad4 AMR exome

AF:

0.00378

Gnomad4 ASJ exome

AF:

0.00417

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000940

Gnomad4 FIN exome

AF:

0.00592

Gnomad4 NFE exome

AF:

0.0141

Gnomad4 OTH exome

AF:

0.00935

GnomAD4 genome

AF:

0.00708

AC:

1079

AN:

152298

Hom.:

Cov.:

AF XY:

0.00651

AC XY:

485

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.00269

Gnomad4 AMR

AF:

0.00399

Gnomad4 ASJ

AF:

0.00346

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00518

Gnomad4 NFE

AF:

0.0121

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00643

Hom.:

Bravo

AF:

0.00685

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00987

EpiControl

AF:

0.0122

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 17, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

8.3

DANN

Benign

0.30

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over