Genetic Variant PPIG:p.Lys231Lys (chr2-169630919-A-G) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_004792.3(PPIG):c.693A>G(p.Lys231Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00157 in 1,603,666 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0012 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0016 ( 4 hom. )

Consequence

PPIG
NM_004792.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.17

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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 2-169630919-A-G is Benign according to our data. Variant chr2-169630919-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2651529.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=3.17 with no splicing effect.

BS2

High AC in GnomAd4 at 188 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPIG	NM_004792.3 link	c.693A>G	p.Lys231Lys	synonymous_variant	Exon 10 of 14	ENST00000260970.8	NP_004783.2	Q13427-1
PPIG	XM_005246966.3 link	c.693A>G	p.Lys231Lys	synonymous_variant	Exon 10 of 14		XP_005247023.1	Q13427-1
PPIG	XM_005246967.2 link	c.693A>G	p.Lys231Lys	synonymous_variant	Exon 10 of 14		XP_005247024.1	Q13427-1
PPIG	XM_017005302.3 link	c.693A>G	p.Lys231Lys	synonymous_variant	Exon 10 of 12		XP_016860791.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPIG	ENST00000260970.8 link	c.693A>G	p.Lys231Lys	synonymous_variant	Exon 10 of 14	1	NM_004792.3	ENSP00000260970.3		Q13427-1

Frequencies

GnomAD3 genomes

AF:

0.00124

AC:

188

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000655

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.000565

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00207

Gnomad OTH

AF:

0.00431

GnomAD3 exomes

AF:

0.00124

AC:

296

AN:

237920

Hom.:

AF XY:

0.00122

AC XY:

157

AN XY:

128952

show subpopulations

Gnomad AFR exome

AF:

0.000328

Gnomad AMR exome

AF:

0.000857

Gnomad ASJ exome

AF:

0.00185

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000335

Gnomad FIN exome

AF:

0.000418

Gnomad NFE exome

AF:

0.00203

Gnomad OTH exome

AF:

0.000853

GnomAD4 exome

AF:

0.00161

AC:

2333

AN:

1451418

Hom.:

Cov.:

AF XY:

0.00161

AC XY:

1162

AN XY:

721496

show subpopulations

Gnomad4 AFR exome

AF:

0.000399

Gnomad4 AMR exome

AF:

0.000814

Gnomad4 ASJ exome

AF:

0.00205

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000375

Gnomad4 FIN exome

AF:

0.000619

Gnomad4 NFE exome

AF:

0.00186

Gnomad4 OTH exome

AF:

0.00143

GnomAD4 genome

AF:

0.00123

AC:

188

AN:

152248

Hom.:

Cov.:

AF XY:

0.00114

AC XY:

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.000240

Gnomad4 AMR

AF:

0.000654

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.000565

Gnomad4 NFE

AF:

0.00207

Gnomad4 OTH

AF:

0.00427

Alfa

AF:

0.00192

Hom.:

Bravo

AF:

0.00121

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Nov 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

PPIG: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.50

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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