Variant 4-158713201-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_005038.3(PPID):c.812T>C(p.Ile271Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000198 in 1,461,580 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

PPID
NM_005038.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.37

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 made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.039031863).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPID	NM_005038.3 linkuse as main transcript	c.812T>C	p.Ile271Thr	missense_variant	7/10	ENST00000307720.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPID	ENST00000307720.4 linkuse as main transcript	c.812T>C	p.Ile271Thr	missense_variant	7/10	1	NM_005038.3	P1
PPID	ENST00000512699.1 linkuse as main transcript	c.*259T>C		3_prime_UTR_variant, NMD_transcript_variant	4/7	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000557

AC:

AN:

251264

Hom.:

AF XY:

0.0000884

AC XY:

AN XY:

135796

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000457

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000198

AC:

AN:

1461580

Hom.:

Cov.:

AF XY:

0.0000275

AC XY:

AN XY:

727094

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000278

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000741

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 28, 2023

The c.812T>C (p.I271T) alteration is located in exon 7 (coding exon 7) of the PPID gene. This alteration results from a T to C substitution at nucleotide position 812, causing the isoleucine (I) at amino acid position 271 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.78

DEOGEN2

Benign

0.0071

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.35

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.66

M_CAP

Benign

0.023

MetaRNN

Benign

0.039

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.3

MutationTaster

Benign

1.0

PrimateAI

Benign

0.31

PROVEAN

Benign

0.050

REVEL

Benign

0.16

Sift

Benign

0.81

Sift4G

Benign

0.76

Polyphen

0.0

Vest4

0.19

MutPred

0.42

Loss of stability (P = 0.0116);

MVP

0.61

MPC

0.22

ClinPred

0.054

GERP RS

5.4

Varity_R

0.055

gMVP

0.19

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