Variant chr5-149358079-C-T 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.11C>T(p.Ala4Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000914 in 1,411,574 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000094 ( 0 hom. )

Consequence

PCYOX1L
NM_024028.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.23

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=0.06884226).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCYOX1L	NM_024028.4 linkuse as main transcript	c.11C>T	p.Ala4Val	missense_variant	1/6	ENST00000274569.9	NP_076933.3	Q8NBM8-1
PCYOX1L	NM_001301054.2 linkuse as main transcript	c.-57C>T		5_prime_UTR_variant	1/6		NP_001287983.1	Q8NBM8
PCYOX1L	NM_001301057.2 linkuse as main transcript	c.-57C>T		5_prime_UTR_variant	1/6		NP_001287986.1	Q8NBM8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PCYOX1L	ENST00000274569.9 linkuse as main transcript	c.11C>T	p.Ala4Val	missense_variant	1/6	2	NM_024028.4	ENSP00000274569.4	Q8NBM8-1
PCYOX1L	ENST00000505669.5 linkuse as main transcript	n.11C>T		non_coding_transcript_exon_variant	1/6	1		ENSP00000427166.1	Q8NBM8-2
PCYOX1L	ENST00000511945.5 linkuse as main transcript	n.11C>T		non_coding_transcript_exon_variant	1/6	1		ENSP00000426091.1	Q8NBM8-2
PCYOX1L	ENST00000510990.6 linkuse as main transcript	n.11C>T		non_coding_transcript_exon_variant	1/5	4		ENSP00000422063.2	D6R9J0

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152048

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000555

AC:

AN:

54052

Hom.:

AF XY:

0.0000634

AC XY:

AN XY:

31552

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000186

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:

0.0000511

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000937

AC:

118

AN:

1259526

Hom.:

Cov.:

AF XY:

0.000104

AC XY:

AN XY:

618124

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000483

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000112

Gnomad4 OTH exome

AF:

0.0000579

GnomAD4 genome

AF:

0.0000723

AC:

AN:

152048

Hom.:

Cov.:

AF XY:

0.0000539

AC XY:

AN XY:

74264

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000642

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

May 31, 2023

The c.11C>T (p.A4V) alteration is located in exon 1 (coding exon 1) of the PCYOX1L gene. This alteration results from a C to T substitution at nucleotide position 11, causing the alanine (A) at amino acid position 4 to be replaced by a valine (V). 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

0.18

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.0010

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.68

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.46

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.069

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PrimateAI

Uncertain

0.79

PROVEAN

Benign

-0.040

REVEL

Benign

0.019

Sift

Benign

0.43

Sift4G

Benign

0.45

Polyphen

0.27

Vest4

0.22

MutPred

0.27

Loss of disorder (P = 0.0206);

MVP

0.14

MPC

0.18

ClinPred

0.043

GERP RS

3.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.022

gMVP

0.44

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