Genetic Variant NM_139126.4:c.1097T>C (chr6-149512285-A-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_139126.4(PPIL4):c.1097T>C(p.Ile366Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000823 in 1,457,908 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

PPIL4
NM_139126.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.60

Variant links:

Genes affected

PPIL4 (HGNC:15702): (peptidylprolyl isomerase like 4) This gene is a member of the cyclophilin family of peptidylprolyl isomerases. The cyclophilins are a highly conserved family, members of which play an important role in protein folding, immunosuppression by cyclosporin A, and infection of HIV-1 virions. [provided by RefSeq, Jul 2008]

PPIL4 links:

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ACMG classification

Classification made for transcript

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=0.10585043).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPIL4	NM_139126.4 link	c.1097T>C	p.Ile366Thr	missense_variant	Exon 12 of 13	ENST00000253329.3	NP_624311.1	Q8WUA2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPIL4	ENST00000253329.3 link	c.1097T>C	p.Ile366Thr	missense_variant	Exon 12 of 13	1	NM_139126.4	ENSP00000253329.2		Q8WUA2
PPIL4	ENST00000340881.2 link	c.-6T>C		5_prime_UTR_variant	Exon 2 of 3	1		ENSP00000344128.2		Q5T4S2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000823

AC:

AN:

1457908

Hom.:

Cov.:

AF XY:

0.00000414

AC XY:

AN XY:

725418

show subpopulations

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:

0.0000108

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000312

Hom.:

Bravo

AF:

0.00000378

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3476

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 30, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1097T>C (p.I366T) alteration is located in exon 12 (coding exon 12) of the PPIL4 gene. This alteration results from a T to C substitution at nucleotide position 1097, causing the isoleucine (I) at amino acid position 366 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.35

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Benign

0.86

DEOGEN2

Benign

0.029

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.069

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.0068

MetaRNN

Benign

0.11

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.81

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.53

REVEL

Benign

0.070

Sift

Benign

0.10

Sift4G

Benign

0.44

Polyphen

0.18

Vest4

0.23

MutPred

0.37

Loss of helix (P = 3e-04);

MVP

0.25

MPC

0.40

ClinPred

0.53

GERP RS

4.8

Varity_R

0.082

gMVP

0.17

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over