Genetic Variant PCYOX1L:p.Pro6Arg (chr5-149358085-C-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_024028.4(PCYOX1L):c.17C>G(p.Pro6Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0005 in 1,433,036 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P6Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00056 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00049 ( 2 hom. )

Consequence

PCYOX1L
NM_024028.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.82

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0034115314).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCYOX1L	NM_024028.4 link	c.17C>G	p.Pro6Arg	missense_variant	Exon 1 of 6	ENST00000274569.9	NP_076933.3	Q8NBM8-1
PCYOX1L	NM_001301054.2 link	c.-51C>G		5_prime_UTR_variant	Exon 1 of 6		NP_001287983.1	Q8NBM8
PCYOX1L	NM_001301057.2 link	c.-51C>G		5_prime_UTR_variant	Exon 1 of 6		NP_001287986.1	Q8NBM8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PCYOX1L	ENST00000274569.9 link	c.17C>G	p.Pro6Arg	missense_variant	Exon 1 of 6	2	NM_024028.4	ENSP00000274569.4	Q8NBM8-1
PCYOX1L	ENST00000505669.5 link	n.17C>G		non_coding_transcript_exon_variant	Exon 1 of 6	1		ENSP00000427166.1	Q8NBM8-2
PCYOX1L	ENST00000511945.5 link	n.17C>G		non_coding_transcript_exon_variant	Exon 1 of 6	1		ENSP00000426091.1	Q8NBM8-2
PCYOX1L	ENST00000510990.6 link	n.17C>G		non_coding_transcript_exon_variant	Exon 1 of 5	4		ENSP00000422063.2	D6R9J0

Frequencies

GnomAD3 genomes

AF:

0.000559

AC:

AN:

152060

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.0188

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00196

AC:

126

AN:

64426

Hom.:

AF XY:

0.00180

AC XY:

AN XY:

37284

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.0195

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000506

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000388

Gnomad OTH exome

AF:

0.00268

GnomAD4 exome

AF:

0.000493

AC:

632

AN:

1280864

Hom.:

Cov.:

AF XY:

0.000480

AC XY:

302

AN XY:

629750

show subpopulations

Gnomad4 AFR exome

AF:

0.0000382

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0204

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000195

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000100

Gnomad4 OTH exome

AF:

0.00140

GnomAD4 genome

AF:

0.000559

AC:

AN:

152172

Hom.:

Cov.:

AF XY:

0.000618

AC XY:

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.0188

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00292

Hom.:

Bravo

AF:

0.000548

ExAC

AF:

0.00148

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.076

DANN

Benign

0.58

DEOGEN2

Benign

0.00084

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.038

LIST_S2

Benign

0.37

MetaRNN

Benign

0.0034

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.0

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-0.16

REVEL

Benign

0.010

Sift

Benign

0.58

Sift4G

Benign

0.57

Polyphen

0.0

Vest4

0.10

MutPred

0.43

Gain of MoRF binding (P = 0);

MVP

0.067

MPC

0.19

ClinPred

0.0045

GERP RS

-5.2

Varity_R

0.025

gMVP

0.26

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over