10-79350661-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005729.4(PPIF):c.316-826G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.629 in 152,160 control chromosomes in the GnomAD database, including 31,657 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 0.63 (31657 hom., cov: 33)
• Consequence: PPIF NM_005729.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.40

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.825 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPIF	NM_005729.4	c.316-826G>C		intron_variant		ENST00000225174.8
PPIF	XM_005269379.3	c.316-826G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPIF	ENST00000225174.8	c.316-826G>C		intron_variant		1	NM_005729.4	P1
PPIF	ENST00000448165.1	c.207-826G>C		intron_variant		2
PPIF	ENST00000472580.6	c.316-826G>C		intron_variant, NMD_transcript_variant		5
PPIF	ENST00000498681.5	n.396-826G>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.628 AC: 95536 AN: 152042 Hom.: 31593 Cov.: 33

Gnomad AFR AF: 0.832

Gnomad AMI AF: 0.496

Gnomad AMR AF: 0.675

Gnomad ASJ AF: 0.457

Gnomad EAS AF: 0.652

Gnomad SAS AF: 0.502

Gnomad FIN AF: 0.603

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.516

Gnomad OTH AF: 0.619

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.629 AC: 95663 AN: 152160 Hom.: 31657 Cov.: 33 AF XY: 0.631 AC XY: 46968 AN XY: 74390

Gnomad4 AFR AF: 0.832

Gnomad4 AMR AF: 0.675

Gnomad4 ASJ AF: 0.457

Gnomad4 EAS AF: 0.652

Gnomad4 SAS AF: 0.502

Gnomad4 FIN AF: 0.603

Gnomad4 NFE AF: 0.516

Gnomad4 OTH AF: 0.621

Alfa AF: 0.575 Hom.: 3122

Bravo AF: 0.645

Asia WGS AF: 0.592 AC: 2058 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	1.0
Dann	Benign	0.76

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

Other links and lift over

dbSNP: rs1316312; hg19: chr10-81110417;