Genetic Variant NM_005729.4:c.98G>A (chr10-79347646-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005729.4(PPIF):c.98G>A(p.Gly33Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000153 in 1,310,698 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G33V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

PPIF
NM_005729.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.08

Publications

0 publications found

Variant links:

Genes affected

PPIF (HGNC:9259): (peptidylprolyl isomerase F) 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 is part of the mitochondrial permeability transition pore in the inner mitochondrial membrane. Activation of this pore is thought to be involved in the induction of apoptotic and necrotic cell death. [provided by RefSeq, Jul 2008]

PPIF links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.088502645).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005729.4. 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
	PPIF	NM_005729.4	MANE Select	c.98G>A	p.Gly33Asp	missense	Exon 1 of 6	NP_005720.1	P30405-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PPIF	ENST00000225174.8	TSL:1 MANE Select	c.98G>A	p.Gly33Asp	missense	Exon 1 of 6	ENSP00000225174.3	P30405-1
PPIF	ENST00000871351.1		c.98G>A	p.Gly33Asp	missense	Exon 1 of 6	ENSP00000541410.1
PPIF	ENST00000955651.1		c.98G>A	p.Gly33Asp	missense	Exon 1 of 6	ENSP00000625710.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000153

AC:

AN:

1310698

Hom.:

Cov.:

AF XY:

0.00000155

AC XY:

AN XY:

646180

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26568

American (AMR)

AF:

0.00

AC:

AN:

24716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22670

East Asian (EAS)

AF:

0.0000360

AC:

AN:

27782

South Asian (SAS)

AF:

0.00

AC:

AN:

70106

European-Finnish (FIN)

AF:

0.00

AC:

AN:

44980

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4638

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1035552

Other (OTH)

AF:

0.0000186

AC:

AN:

53686

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

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.:

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.70

CADD

Benign

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.24

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.45

M_CAP

Benign

0.012

MetaRNN

Benign

0.089

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

PhyloP100

1.1

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-0.77

REVEL

Benign

0.035

Sift

Benign

0.13

Sift4G

Benign

0.17

Polyphen

0.0

Vest4

0.15

MutPred

0.22

Loss of helix (P = 0.0558)

MVP

0.38

MPC

1.4

ClinPred

0.087

GERP RS

0.096

PromoterAI

0.045

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.13

gMVP

0.51

Mutation Taster

=98/2

polymorphism

(source)

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

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