Genetic Variant PPIF:c.*1215C>G (chr10-79355057-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005729.4(PPIF):c.*1215C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.649 in 152,064 control chromosomes in the GnomAD database, including 34,258 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.65 ( 34258 hom., cov: 32)

Exomes 𝑓: 0.53 ( 19 hom. )

Failed GnomAD Quality Control

Consequence

PPIF
NM_005729.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0370

Publications

11 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.892 is higher than 0.05.

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.*1215C>G		3_prime_UTR	Exon 6 of 6	NP_005720.1	P30405-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PPIF	ENST00000225174.8	TSL:1 MANE Select	c.*1215C>G	3_prime_UTR	Exon 6 of 6	ENSP00000225174.3	P30405-1
PPIF	ENST00000871351.1		c.*1215C>G	3_prime_UTR	Exon 6 of 6	ENSP00000541410.1
PPIF	ENST00000955651.1		c.*1215C>G	3_prime_UTR	Exon 6 of 6	ENSP00000625710.1

Frequencies

GnomAD3 genomes

AF:

0.649

AC:

98582

AN:

151944

Hom.:

34190

Cov.:

show subpopulations

Gnomad AFR

AF:

0.899

Gnomad AMI

AF:

0.496

Gnomad AMR

AF:

0.684

Gnomad ASJ

AF:

0.461

Gnomad EAS

AF:

0.655

Gnomad SAS

AF:

0.512

Gnomad FIN

AF:

0.602

Gnomad MID

AF:

0.560

Gnomad NFE

AF:

0.517

Gnomad OTH

AF:

0.632

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.529

AC:

AN:

140

Hom.:

Cov.:

AF XY:

0.512

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.554

AC:

AN:

130

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.250

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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

AF:

0.649

AC:

98712

AN:

152064

Hom.:

34258

Cov.:

AF XY:

0.651

AC XY:

48350

AN XY:

74288

show subpopulations

African (AFR)

AF:

0.900

AC:

37350

AN:

41516

American (AMR)

AF:

0.684

AC:

10457

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.461

AC:

1597

AN:

3466

East Asian (EAS)

AF:

0.655

AC:

3386

AN:

5166

South Asian (SAS)

AF:

0.511

AC:

2464

AN:

4820

European-Finnish (FIN)

AF:

0.602

AC:

6348

AN:

10544

Middle Eastern (MID)

AF:

0.558

AC:

164

AN:

294

European-Non Finnish (NFE)

AF:

0.517

AC:

35155

AN:

67954

Other (OTH)

AF:

0.634

AC:

1339

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1568

3135

4703

6270

7838

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

770

1540

2310

3080

3850

<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:

0.431

Hom.:

1121

Bravo

AF:

0.668

Asia WGS

AF:

0.609

AC:

2117

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.55

(source)

DANN

Benign

0.40

PhyloP100

0.037

Mutation Taster

=100/0

polymorphism (auto)

(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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over