rs762017805

Variant names:

• chr10-79352358-T-A
• rs762017805
• NM_005729.4:c.454T>A

Your query was ambiguous. Multiple possible variants found:

• chr10-79352358-T-A
• chr10-79352358-T-G

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_005729.4(PPIF):​c.454T>A​(p.Ser152Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PPIF NM_005729.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.02

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 Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.976

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPIF	NM_005729.4	c.454T>A	p.Ser152Thr	missense_variant	Exon 5 of 6	ENST00000225174.8	NP_005720.1
PPIF	XM_005269379.3	c.454T>A	p.Ser152Thr	missense_variant	Exon 5 of 6		XP_005269436.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPIF	ENST00000225174.8	c.454T>A	p.Ser152Thr	missense_variant	Exon 5 of 6	1	NM_005729.4	ENSP00000225174.3
PPIF	ENST00000448165.1	c.343T>A	p.Ser115Thr	missense_variant	Exon 5 of 6	2		ENSP00000396388.1
PPIF	ENST00000472580.6	n.*147T>A		non_coding_transcript_exon_variant	Exon 5 of 6	5		ENSP00000473548.1
PPIF	ENST00000472580.6	n.*147T>A		3_prime_UTR_variant	Exon 5 of 6	5		ENSP00000473548.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.92
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.17
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.32	T
Eigen	Pathogenic	1.0
Eigen_PC	Pathogenic	0.92
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.057	D
MetaRNN	Pathogenic	0.98	D
MetaSVM	Uncertain	0.29	D
MutationAssessor	Pathogenic	3.5	H
PrimateAI	Uncertain	0.76	T
PROVEAN	Uncertain	-2.9	D
REVEL	Uncertain	0.63
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.99	D
Vest4		0.90
MutPred		0.93		Loss of disorder (P = 0.1154);
MVP		0.94
MPC		0.32
ClinPred		0.99	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.93
gMVP		0.78

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: rs762017805; hg19: chr10-81112114;