Genetic Variant PPID:p.His146ArgfsTer8 (chr4-158717095-CAT-C) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_005038.3(PPID):c.437_438delAT(p.His146ArgfsTer8) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00128 in 1,614,098 control chromosomes in the GnomAD database, including 9 homozygotes. Variant has been reported in ClinVar as Likely benign (★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0013 ( 9 hom. )

Consequence

PPID
NM_005038.3 frameshift

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.67

Publications

4 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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP6

Variant 4-158717095-CAT-C is Benign according to our data. Variant chr4-158717095-CAT-C is described in ClinVar as Likely_benign. ClinVar VariationId is 711202.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 9 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005038.3. 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
	PPID	NM_005038.3	MANE Select	c.437_438delAT	p.His146ArgfsTer8	frameshift	Exon 4 of 10	NP_005029.1	E5KN55

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PPID	ENST00000307720.4	TSL:1 MANE Select	c.437_438delAT	p.His146ArgfsTer8	frameshift	Exon 4 of 10	ENSP00000303754.3	Q08752
PPID	ENST00000877683.1		c.419_420delAT	p.His140ArgfsTer8	frameshift	Exon 4 of 10	ENSP00000547742.1
PPID	ENST00000877682.1		c.437_438delAT	p.His146ArgfsTer8	frameshift	Exon 4 of 10	ENSP00000547741.1

Frequencies

GnomAD3 genomes

AF:

0.00120

AC:

183

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000892

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00548

Gnomad EAS

AF:

0.0111

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000720

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.00159

AC:

400

AN:

251408

AF XY:

0.00149

show subpopulations

Gnomad AFR exome

AF:

0.000984

Gnomad AMR exome

AF:

0.00110

Gnomad ASJ exome

AF:

0.00456

Gnomad EAS exome

AF:

0.00854

Gnomad FIN exome

AF:

0.000601

Gnomad NFE exome

AF:

0.000765

Gnomad OTH exome

AF:

0.000815

GnomAD4 exome

AF:

0.00129

AC:

1889

AN:

1461742

Hom.:

AF XY:

0.00126

AC XY:

913

AN XY:

727194

show subpopulations

African (AFR)

AF:

0.00108

AC:

AN:

33474

American (AMR)

AF:

0.00127

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00398

AC:

104

AN:

26136

East Asian (EAS)

AF:

0.0139

AC:

552

AN:

39698

South Asian (SAS)

AF:

0.00128

AC:

110

AN:

86248

European-Finnish (FIN)

AF:

0.000505

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00191

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000804

AC:

894

AN:

1111886

Other (OTH)

AF:

0.00162

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

106

212

318

424

530

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

114

152

190

<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:

0.00119

AC:

182

AN:

152356

Hom.:

Cov.:

AF XY:

0.00132

AC XY:

AN XY:

74504

show subpopulations

African (AFR)

AF:

0.000890

AC:

AN:

41582

American (AMR)

AF:

0.000457

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00548

AC:

AN:

3470

East Asian (EAS)

AF:

0.0108

AC:

AN:

5192

South Asian (SAS)

AF:

0.00207

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.000283

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000720

AC:

AN:

68034

Other (OTH)

AF:

0.000473

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000441

Hom.:

Bravo

AF:

0.00108

Asia WGS

AF:

0.00722

AC:

AN:

3478

EpiCase

AF:

0.000545

EpiControl

AF:

0.000534

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

7.7

Mutation Taster

=15/185

disease causing (fs/PTC)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over