Variant 5-149358085-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_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. 14/21 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

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PCYOX1L	NM_024028.4 linkuse as main transcript	c.17C>A	p.Pro6Gln	missense_variant	1/6	ENST00000274569.9
PCYOX1L	NM_001301054.2 linkuse as main transcript	c.-51C>A		5_prime_UTR_variant	1/6
PCYOX1L	NM_001301057.2 linkuse as main transcript	c.-51C>A		5_prime_UTR_variant	1/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCYOX1L	ENST00000274569.9 linkuse as main transcript	c.17C>A	p.Pro6Gln	missense_variant	1/6	2	NM_024028.4	P1	Q8NBM8-1
PCYOX1L	ENST00000505669.5 linkuse as main transcript	c.17C>A	p.Pro6Gln	missense_variant, NMD_transcript_variant	1/6	1			Q8NBM8-2
PCYOX1L	ENST00000511945.5 linkuse as main transcript	c.17C>A	p.Pro6Gln	missense_variant, NMD_transcript_variant	1/6	1			Q8NBM8-2
PCYOX1L	ENST00000510990.6 linkuse as main transcript	c.17C>A	p.Pro6Gln	missense_variant, NMD_transcript_variant	1/5	4

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

GnomAD3 exomes

AF:

0.0000155

AC:

AN:

64426

Hom.:

AF XY:

0.0000268

AC XY:

AN XY:

37284

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 SAS exome

AF:

0.0000723

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

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000171

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000135

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.74e-7

Gnomad4 OTH exome

AF:

0.0000568

GnomAD4 genome

AF:

0.000105

AC:

AN:

152060

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74288

show subpopulations

Gnomad4 AFR

AF:

0.0000965

Gnomad4 AMR

AF:

0.000720

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000478

Bravo

AF:

0.000166

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

Sep 27, 2022

The c.17C>A (p.P6Q) alteration is located in exon 1 (coding exon 1) of the PCYOX1L gene. This alteration results from a C to A substitution at nucleotide position 17, causing the proline (P) at amino acid position 6 to be replaced by a glutamine (Q). 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

0.17

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.73

Cadd

Benign

0.084

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

MutationTaster

Benign

1.0

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

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.022

gMVP

0.22

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