dbSNP rs61756415: PPID:p.Val177Phe (chr4-158715678-C-A) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_005038.3(PPID):c.529G>T(p.Val177Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,456,088 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V177I) has been classified as Benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

PPID
NM_005038.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.309

Publications

0 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPID	NM_005038.3	MANE Select	c.529G>T	p.Val177Phe	missense	Exon 5 of 10	NP_005029.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPID	ENST00000307720.4	TSL:1 MANE Select	c.529G>T	p.Val177Phe	missense	Exon 5 of 10	ENSP00000303754.3
	PPID	ENST00000512699.1	TSL:3	n.43-10G>T		intron	N/A	ENSP00000423207.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1456088

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

724686

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33324

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26110

East Asian (EAS)

AF:

0.00

AC:

AN:

39648

South Asian (SAS)

AF:

0.00

AC:

AN:

86146

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53392

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

9.04e-7

AC:

AN:

1106774

Other (OTH)

AF:

0.00

AC:

AN:

60206

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Benign

8.5

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.052

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.83

FATHMM_MKL

Benign

0.45

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.028

MetaRNN

Uncertain

0.52

MetaSVM

Benign

-0.81

MutationAssessor

Uncertain

2.8

PhyloP100

-0.31

PrimateAI

Benign

0.27

PROVEAN

Uncertain

-3.0

REVEL

Benign

0.20

Sift

Uncertain

0.011

Sift4G

Benign

0.13

Polyphen

0.94

Vest4

0.64

MutPred

0.45

Gain of ubiquitination at K174 (P = 0.1181)

MVP

0.28

MPC

0.63

ClinPred

0.99

GERP RS

-4.3

Varity_R

0.35

gMVP

0.75

Mutation Taster

=85/15

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.55

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.55

Position offset: 6

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over