10-79355057-C-G

Variant names:

• chr10-79355057-C-G
• rs8837
• NM_005729.4:c.*1215C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0370

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: 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPIF	NM_005729.4	c.*1215C>G		3_prime_UTR_variant	Exon 6 of 6	ENST00000225174.8	NP_005720.1
PPIF	XM_005269379.3	c.*1295C>G		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.*1215C>G		3_prime_UTR_variant	Exon 6 of 6	1	NM_005729.4	ENSP00000225174.3

Frequencies

GnomAD3 genomes AF: 0.649 AC: 98582 AN: 151944 Hom.: 34190 Cov.: 32

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: 74 AN: 140 Hom.: 19 Cov.: 0 AF XY: 0.512 AC XY: 41 AN XY: 80

Gnomad4 AFR exome AC: 0 AN: 0

Gnomad4 AMR exome AC: 0 AN: 0

Gnomad4 ASJ exome AC: 0 AN: 0

Gnomad4 EAS exome AF: 0.554 AC: 72 AN: 130

Gnomad4 SAS exome AF: 0.00 AC: 0 AN: 2

Gnomad4 FIN exome AC: 0 AN: 0

Gnomad4 NFE exome AF: 0.250 AC: 2 AN: 8

Gnomad4 Remaining exome AC: 0 AN: 0

GnomAD4 genome AF: 0.649 AC: 98712 AN: 152064 Hom.: 34258 Cov.: 32 AF XY: 0.651 AC XY: 48350 AN XY: 74288

Gnomad4 AFR AF: 0.900 AC: 0.899653 AN: 0.899653

Gnomad4 AMR AF: 0.684 AC: 0.684359 AN: 0.684359

Gnomad4 ASJ AF: 0.461 AC: 0.460762 AN: 0.460762

Gnomad4 EAS AF: 0.655 AC: 0.655439 AN: 0.655439

Gnomad4 SAS AF: 0.511 AC: 0.511203 AN: 0.511203

Gnomad4 FIN AF: 0.602 AC: 0.602049 AN: 0.602049

Gnomad4 NFE AF: 0.517 AC: 0.517335 AN: 0.517335

Gnomad4 OTH AF: 0.634 AC: 0.633996 AN: 0.633996

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.55
DANN	Benign	0.40
Mutation Taster		=100/0	polymorphism (auto)

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: rs8837; hg19: chr10-81114813;