4-158717149-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_005038.3(PPID):c.385G>A(p.Gly129Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000551 in 1,613,980 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000072 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000053 ( 0 hom. )
Consequence
PPID
NM_005038.3 missense
NM_005038.3 missense
Scores
3
9
7
Clinical Significance
Conservation
PhyloP100: 7.57
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.832
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PPID | NM_005038.3 | c.385G>A | p.Gly129Ser | missense_variant | 4/10 | ENST00000307720.4 | NP_005029.1 | |
PPID | XM_047415844.1 | c.385G>A | p.Gly129Ser | missense_variant | 4/5 | XP_047271800.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PPID | ENST00000307720.4 | c.385G>A | p.Gly129Ser | missense_variant | 4/10 | 1 | NM_005038.3 | ENSP00000303754 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000723 AC: 11AN: 152112Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000318 AC: 8AN: 251434Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135898
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GnomAD4 exome AF: 0.0000534 AC: 78AN: 1461868Hom.: 0 Cov.: 31 AF XY: 0.0000564 AC XY: 41AN XY: 727240
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GnomAD4 genome AF: 0.0000723 AC: 11AN: 152112Hom.: 0 Cov.: 33 AF XY: 0.0000673 AC XY: 5AN XY: 74284
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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 | May 24, 2024 | The c.385G>A (p.G129S) alteration is located in exon 4 (coding exon 4) of the PPID gene. This alteration results from a G to A substitution at nucleotide position 385, causing the glycine (G) at amino acid position 129 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Benign
D
MetaRNN
Pathogenic
D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at