Genetic Variant PCYOX1L:p.Pro6Gln (chr5-149358085-C-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_024028.4(PCYOX1L):c.17C>A(p.Pro6Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000023 in 1,432,942 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

PCYOX1L
NM_024028.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

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: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.03196001).

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>A	p.Pro6Gln	missense	Exon 1 of 6	NP_076933.3
PCYOX1L	NM_001301054.2		c.-51C>A		5_prime_UTR	Exon 1 of 6	NP_001287983.1
PCYOX1L	NM_001301057.2		c.-51C>A		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>A	p.Pro6Gln	missense	Exon 1 of 6	ENSP00000274569.4	Q8NBM8-1
PCYOX1L	ENST00000505669.5	TSL:1	n.17C>A		non_coding_transcript_exon	Exon 1 of 6	ENSP00000427166.1	Q8NBM8-2
PCYOX1L	ENST00000511945.5	TSL:1	n.17C>A		non_coding_transcript_exon	Exon 1 of 6	ENSP00000426091.1	Q8NBM8-2

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152060

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

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:

0.00

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.0000155

AC:

AN:

64426

AF XY:

0.0000268

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000133

AC:

AN:

1280882

Hom.:

Cov.:

AF XY:

0.0000143

AC XY:

AN XY:

629758

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26150

American (AMR)

AF:

0.000171

AC:

AN:

23364

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21498

East Asian (EAS)

AF:

0.00

AC:

AN:

27456

South Asian (SAS)

AF:

0.000135

AC:

AN:

66692

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32162

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3746

European-Non Finnish (NFE)

AF:

9.74e-7

AC:

AN:

1027022

Other (OTH)

AF:

0.0000568

AC:

AN:

52792

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.566

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.000105

AC:

AN:

152060

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74288

show subpopulations

African (AFR)

AF:

0.0000965

AC:

AN:

41430

American (AMR)

AF:

0.000720

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10576

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67978

Other (OTH)

AF:

0.000478

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

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:

0.00

Hom.:

Bravo

AF:

0.000166

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.73

CADD

Benign

0.084

(source)

DANN

Benign

0.75

DEOGEN2

Benign

0.00084

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.082

LIST_S2

Benign

0.31

M_CAP

Benign

0.030

MetaRNN

Benign

0.032

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.0

PhyloP100

-2.8

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-0.090

REVEL

Benign

0.013

Sift

Benign

0.52

Sift4G

Benign

0.47

Polyphen

0.0

Vest4

0.14

MutPred

0.36

Gain of MoRF binding (P = 0.0056)

MVP

0.055

MPC

0.17

ClinPred

0.027

GERP RS

-5.2

PromoterAI

-0.018

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.022

gMVP

0.22

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