Variant 5-149364080-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_024028.4(PCYOX1L):c.340G>A(p.Gly114Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,613,960 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

PCYOX1L
NM_024028.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.70

Variant links:

Genes affected

PCYOX1L (HGNC:28477): (prenylcysteine oxidase 1 like) Predicted to enable prenylcysteine oxidase activity. Predicted to be involved in prenylated protein catabolic process. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

PCYOX1L links:

Genome browser will be placed here

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=0.18541962).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PCYOX1L	NM_024028.4 linkuse as main transcript	c.340G>A	p.Gly114Ser	missense_variant	3/6	ENST00000274569.9
PCYOX1L	NM_001301054.2 linkuse as main transcript	c.289G>A	p.Gly97Ser	missense_variant	3/6
PCYOX1L	NM_001301057.2 linkuse as main transcript	c.289G>A	p.Gly97Ser	missense_variant	3/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCYOX1L	ENST00000274569.9 linkuse as main transcript	c.340G>A	p.Gly114Ser	missense_variant	3/6	2	NM_024028.4	P1	Q8NBM8-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000159

AC:

AN:

251268

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135804

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000867

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1461808

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727202

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152152

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74300

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.00000824

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 08, 2023

The c.340G>A (p.G114S) alteration is located in exon 3 (coding exon 3) of the PCYOX1L gene. This alteration results from a G to A substitution at nucleotide position 340, causing the glycine (G) at amino acid position 114 to be replaced by a serine (S). 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

0.059

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.74

Cadd

Benign

Dann

Benign

0.95

DEOGEN2

Benign

0.00066

T;.

Eigen

Benign

-0.86

Eigen_PC

Benign

-0.71

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.74

T;T

M_CAP

Benign

0.0023

MetaRNN

Benign

0.19

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-0.14

N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

0.89

N;N

REVEL

Benign

0.038

Sift

Benign

0.20

T;T

Sift4G

Benign

0.27

T;T

Polyphen

0.013

B;B

Vest4

0.22

MutPred

0.55

Gain of glycosylation at G114 (P = 0.0332);.;

MVP

0.23

MPC

0.18

ClinPred

0.067

GERP RS

2.7

Varity_R

0.033

gMVP

0.48

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