Genetic Variant PPID:c.-61G>A (chr4-158723349-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005038.3(PPID):c.-61G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 1,517,194 control chromosomes in the GnomAD database, including 65,337 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.27 ( 5911 hom., cov: 32)

Exomes 𝑓: 0.29 ( 59426 hom. )

Consequence

PPID
NM_005038.3 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.87

Publications

16 publications found

Variant links:

Genes affected

PPID (HGNC:9257): (peptidylprolyl isomerase D) The protein encoded by this gene is a member of the peptidyl-prolyl cis-trans isomerase (PPIase) family. PPIases catalyze the cis-trans isomerization of proline imidic peptide bonds in oligopeptides and accelerate the folding of proteins. This protein has been shown to possess PPIase activity and, similar to other family members, can bind to the immunosuppressant cyclosporin A. [provided by RefSeq, Jul 2008]

PPID links:

ENSG00000294185 (HGNC:):

ENSG00000294185 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.03).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.303 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPID	NM_005038.3 link	c.-61G>A		5_prime_UTR_variant	Exon 1 of 10	ENST00000307720.4	NP_005029.1
PPID	XM_047415844.1 link	c.-61G>A		5_prime_UTR_variant	Exon 1 of 5		XP_047271800.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPID	ENST00000307720.4 link	c.-61G>A		5_prime_UTR_variant	Exon 1 of 10	1	NM_005038.3	ENSP00000303754.3
ENSG00000294185	ENST00000721785.1 link	n.-112C>T		upstream_gene_variant

Frequencies

GnomAD3 genomes

AF:

0.274

AC:

41598

AN:

151874

Hom.:

5905

Cov.:

show subpopulations

Gnomad AFR

AF:

0.292

Gnomad AMI

AF:

0.156

Gnomad AMR

AF:

0.202

Gnomad ASJ

AF:

0.273

Gnomad EAS

AF:

0.134

Gnomad SAS

AF:

0.316

Gnomad FIN

AF:

0.244

Gnomad MID

AF:

0.241

Gnomad NFE

AF:

0.293

Gnomad OTH

AF:

0.271

GnomAD4 exome

AF:

0.291

AC:

397796

AN:

1365202

Hom.:

59426

Cov.:

AF XY:

0.292

AC XY:

199604

AN XY:

682820

show subpopulations

African (AFR)

AF:

0.291

AC:

9080

AN:

31154

American (AMR)

AF:

0.138

AC:

5869

AN:

42588

Ashkenazi Jewish (ASJ)

AF:

0.273

AC:

6877

AN:

25200

East Asian (EAS)

AF:

0.164

AC:

6299

AN:

38304

South Asian (SAS)

AF:

0.322

AC:

26774

AN:

83068

European-Finnish (FIN)

AF:

0.257

AC:

12931

AN:

50342

Middle Eastern (MID)

AF:

0.264

AC:

1467

AN:

5550

European-Non Finnish (NFE)

AF:

0.303

AC:

312495

AN:

1031836

Other (OTH)

AF:

0.280

AC:

16004

AN:

57160

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

14264

28529

42793

57058

71322

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10122

20244

30366

40488

50610

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.274

AC:

41621

AN:

151992

Hom.:

5911

Cov.:

AF XY:

0.267

AC XY:

19821

AN XY:

74270

show subpopulations

African (AFR)

AF:

0.292

AC:

12117

AN:

41446

American (AMR)

AF:

0.202

AC:

3086

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.273

AC:

947

AN:

3470

East Asian (EAS)

AF:

0.134

AC:

692

AN:

5178

South Asian (SAS)

AF:

0.316

AC:

1521

AN:

4816

European-Finnish (FIN)

AF:

0.244

AC:

2582

AN:

10566

Middle Eastern (MID)

AF:

0.235

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.293

AC:

19900

AN:

67900

Other (OTH)

AF:

0.268

AC:

565

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

1611

3222

4834

6445

8056

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

436

872

1308

1744

2180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.251

Hom.:

2603

Bravo

AF:

0.270

Asia WGS

AF:

0.214

AC:

746

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

2.2

(source)

DANN

Benign

0.92

PhyloP100

-2.9

PromoterAI

0.047

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=300/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over