Variant 6-109403058-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001111298.2(PPIL6):c.739G>C(p.Gly247Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000145 in 1,380,476 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: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

PPIL6
NM_001111298.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.776

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPIL6	NM_173672.5 linkuse as main transcript	c.689-2888G>C		intron_variant		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.689-2888G>C		intron_variant		1	NM_173672.5	ENSP00000427929.1		Q8IXY8-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000749

AC:

AN:

133458

Hom.:

AF XY:

0.00

AC XY:

AN XY:

72730

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000980

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000145

AC:

AN:

1380476

Hom.:

Cov.:

AF XY:

0.00000147

AC XY:

AN XY:

681316

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000564

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jan 29, 2024

The c.739G>C (p.G247R) alteration is located in exon 7 (coding exon 7) of the PPIL6 gene. This alteration results from a G to C substitution at nucleotide position 739, causing the glycine (G) at amino acid position 247 to be replaced by an arginine (R). 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

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Uncertain

1.0

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.60

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.52

M_CAP

Benign

0.0018

MetaRNN

Benign

0.15

MetaSVM

Benign

-1.1

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.17

REVEL

Benign

0.045

Sift

Pathogenic

0.0

Sift4G

Benign

0.095

Vest4

0.23

MutPred

0.34

Gain of solvent accessibility (P = 0.0097);

MVP

0.19

MPC

0.17

ClinPred

0.54

GERP RS

0.77

gMVP

0.43

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.35

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.35

Position offset: 50

DS_DG_spliceai

0.35

Position offset: -27

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