rs756817544

Variant names:

• chr10-79347646-G-A
• rs756817544
• NM_005729.4:c.98G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-79347646-G-A
• chr10-79347646-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.08
• Publications: 0 publications found

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

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

Sel.	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.: 32

GnomAD4 exome AF: 0.00000153 AC: 2 AN: 1310698 Hom.: 0 Cov.: 31 AF XY: 0.00000155 AC XY: 1 AN XY: 646180

African (AFR) AF: 0.00 AC: 0 AN: 26568

American (AMR) AF: 0.00 AC: 0 AN: 24716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22670

East Asian (EAS) AF: 0.0000360 AC: 1 AN: 27782

South Asian (SAS) AF: 0.00 AC: 0 AN: 70106

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44980

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4638

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1035552

Other (OTH) AF: 0.0000186 AC: 1 AN: 53686

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	18
DANN	Benign	0.90
DEOGEN2	Benign	0.24	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.089	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PhyloP100		1.1
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-0.77	N
REVEL	Benign	0.035
Sift	Benign	0.13	T
Sift4G	Benign	0.17	T
Polyphen		0.0	B
Vest4		0.15
MutPred		0.22		Loss of helix (P = 0.0558)
MVP		0.38
MPC		1.4
ClinPred		0.087	T
GERP RS		0.096
PromoterAI		0.045	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.13
gMVP		0.51
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs756817544; hg19: chr10-81107402;