Variant 6-109440496-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_173672.5(PPIL6):c.95T>A(p.Phe32Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000151 in 1,538,916 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00015 ( 0 hom. )

Consequence

PPIL6
NM_173672.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.90

Variant links:

Genes affected

PPIL6 (HGNC:21557): (peptidylprolyl isomerase like 6) Predicted to enable peptidyl-prolyl cis-trans isomerase activity. Predicted to be involved in protein folding and protein peptidyl-prolyl isomerization. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

PPIL6 links:

PPIL6 (HGNC:):

PPIL6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.056846827).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPIL6	NM_173672.5 linkuse as main transcript	c.95T>A	p.Phe32Tyr	missense_variant	1/8	ENST00000521072.7	NP_775943.1	Q8IXY8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPIL6	ENST00000521072.7 linkuse as main transcript	c.95T>A	p.Phe32Tyr	missense_variant	1/8	1	NM_173672.5	ENSP00000427929.1		Q8IXY8-1

Frequencies

GnomAD3 genomes

AF:

0.000158

AC:

AN:

151926

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.000481

GnomAD3 exomes

AF:

0.000145

AC:

AN:

138036

Hom.:

AF XY:

0.000121

AC XY:

AN XY:

74428

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000212

Gnomad ASJ exome

AF:

0.000253

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000135

Gnomad NFE exome

AF:

0.000157

Gnomad OTH exome

AF:

0.000754

GnomAD4 exome

AF:

0.000150

AC:

208

AN:

1386878

Hom.:

Cov.:

AF XY:

0.000146

AC XY:

100

AN XY:

684120

show subpopulations

Gnomad4 AFR exome

AF:

0.0000336

Gnomad4 AMR exome

AF:

0.000257

Gnomad4 ASJ exome

AF:

0.000243

Gnomad4 EAS exome

AF:

0.0000289

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000294

Gnomad4 NFE exome

AF:

0.000155

Gnomad4 OTH exome

AF:

0.000174

GnomAD4 genome

AF:

0.000158

AC:

AN:

152038

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.000476

Alfa

AF:

0.000136

Hom.:

Bravo

AF:

0.000223

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000140

AC:

ExAC

AF:

0.0000956

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 16, 2023

The c.95T>A (p.F32Y) alteration is located in exon 1 (coding exon 1) of the PPIL6 gene. This alteration results from a T to A substitution at nucleotide position 95, causing the phenylalanine (F) at amino acid position 32 to be replaced by a tyrosine (Y). 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

Benign

0.20

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.24

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.023

T;.;.;T

Eigen

Uncertain

0.21

Eigen_PC

Benign

0.15

FATHMM_MKL

Benign

0.27

LIST_S2

Benign

0.51

T;T;T;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.057

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.5

M;M;M;.

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-0.79

N;N;N;N

REVEL

Benign

0.070

Sift

Uncertain

0.013

D;D;D;T

Sift4G

Uncertain

0.0030

D;D;D;.

Polyphen

0.98

D;.;.;.

Vest4

0.28

MVP

0.14

MPC

0.10

ClinPred

0.71

GERP RS

4.1

Varity_R

0.38

gMVP

0.50

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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