rs2230224

Variant names:

• chr10-79353779-C-A
• NM_005729.4:c.561C>A

Your query was ambiguous. Multiple possible variants found:

• chr10-79353779-C-A
• chr10-79353779-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005729.4(PPIF):​c.561C>A​(p.Phe187Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PPIF NM_005729.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08265495).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPIF	NM_005729.4	c.561C>A	p.Phe187Leu	missense_variant	Exon 6 of 6	ENST00000225174.8	NP_005720.1
PPIF	XM_005269379.3	c.*17C>A		3_prime_UTR_variant	Exon 6 of 6		XP_005269436.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPIF	ENST00000225174.8	c.561C>A	p.Phe187Leu	missense_variant	Exon 6 of 6	1	NM_005729.4	ENSP00000225174.3
PPIF	ENST00000448165.1	c.*17C>A		3_prime_UTR_variant	Exon 6 of 6	2		ENSP00000396388.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461890 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727246

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.75
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	0.10
DANN	Uncertain	0.98
DEOGEN2	Benign	0.17	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.0098	T
MetaRNN	Benign	0.083	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-2.0	N
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.052
Sift	Benign	0.15	T
Sift4G	Benign	0.23	T
Polyphen		0.030	B
Vest4		0.13
MutPred		0.22		Loss of methylation at K183 (P = 0.0975);
MVP		0.42
MPC		0.055
ClinPred		0.26	T
GERP RS		-5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.41
gMVP		0.31

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-81113535;