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

Variant summary

Our verdict is Benign. The variant received -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. 14/21 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

Publications

0 publications found

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:

GRPEL2-AS1 (HGNC:48999): (GRPEL2 antisense RNA 1)

GRPEL2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

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

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024028.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PCYOX1L	NM_024028.4	MANE Select	c.17C>G	p.Pro6Arg	missense	Exon 1 of 6	NP_076933.3
PCYOX1L	NM_001301054.2		c.-51C>G		5_prime_UTR	Exon 1 of 6	NP_001287983.1
PCYOX1L	NM_001301057.2		c.-51C>G		5_prime_UTR	Exon 1 of 6	NP_001287986.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PCYOX1L	ENST00000274569.9	TSL:2 MANE Select	c.17C>G	p.Pro6Arg	missense	Exon 1 of 6	ENSP00000274569.4	Q8NBM8-1
PCYOX1L	ENST00000505669.5	TSL:1	n.17C>G		non_coding_transcript_exon	Exon 1 of 6	ENSP00000427166.1	Q8NBM8-2
PCYOX1L	ENST00000511945.5	TSL:1	n.17C>G		non_coding_transcript_exon	Exon 1 of 6	ENSP00000426091.1	Q8NBM8-2

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

GnomAD2 exomes

AF:

0.00196

AC:

126

AN:

64426

AF XY:

0.00180

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 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

African (AFR)

AF:

0.0000382

AC:

AN:

26150

American (AMR)

AF:

0.00

AC:

AN:

23364

Ashkenazi Jewish (ASJ)

AF:

0.0204

AC:

439

AN:

21484

East Asian (EAS)

AF:

0.00

AC:

AN:

27456

South Asian (SAS)

AF:

0.000195

AC:

AN:

66692

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32162

Middle Eastern (MID)

AF:

0.000534

AC:

AN:

3746

European-Non Finnish (NFE)

AF:

0.000100

AC:

103

AN:

1027022

Other (OTH)

AF:

0.00140

AC:

AN:

52788

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

106

141

176

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000559

AC:

AN:

152172

Hom.:

Cov.:

AF XY:

0.000618

AC XY:

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41548

American (AMR)

AF:

0.00

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0188

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.000414

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10576

Middle Eastern (MID)

AF:

0.00342

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000235

AC:

AN:

67970

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00292

Hom.:

Bravo

AF:

0.000548

ExAC

AF:

0.00148

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.076

(source)

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

PhyloP100

-2.8

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

PromoterAI

0.072

Neutral

(source)

Varity_R

0.025

gMVP

0.26

Mutation Taster

=94/6

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over