Variant 2-70259398-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_016297.4(PCYOX1):c.151T>C(p.Tyr51His) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,834 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

PCYOX1
NM_016297.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.91

Variant links:

Genes affected

PCYOX1 (HGNC:20588): (prenylcysteine oxidase 1) Prenylcysteine is released during the degradation of prenylated proteins. PCYOX1 catalyzes the degradation of prenylcysteine to yield free cysteines and a hydrophobic isoprenoid product (Tschantz et al., 1999 [PubMed 10585463]).[supplied by OMIM, Mar 2008]

PCYOX1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCYOX1	NM_016297.4 linkuse as main transcript	c.151T>C	p.Tyr51His	missense_variant	2/6	ENST00000433351.7	NP_057381.3	Q9UHG3-1
PCYOX1	XM_047444689.1 linkuse as main transcript	c.-81T>C		5_prime_UTR_variant	2/6		XP_047300645.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCYOX1	ENST00000433351.7 linkuse as main transcript	c.151T>C	p.Tyr51His	missense_variant	2/6	1	NM_016297.4	ENSP00000387654.2		Q9UHG3-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251476

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135920

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000163

Gnomad SAS 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:

0.00000274

AC:

AN:

1461834

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000151

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

Feb 23, 2023

The c.151T>C (p.Y51H) alteration is located in exon 2 (coding exon 2) of the PCYOX1 gene. This alteration results from a T to C substitution at nucleotide position 151, causing the tyrosine (Y) at amino acid position 51 to be replaced by a histidine (H). 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

0.19

BayesDel_addAF

Benign

0.0067

BayesDel_noAF

Uncertain

0.040

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.13

T;.

Eigen

Uncertain

0.28

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.94

D;D

M_CAP

Benign

0.073

MetaRNN

Uncertain

0.57

D;D

MetaSVM

Uncertain

-0.22

MutationAssessor

Benign

0.83

L;.

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-1.4

N;N

REVEL

Pathogenic

0.66

Sift

Benign

0.85

T;T

Sift4G

Benign

0.65

T;T

Polyphen

0.99

D;.

Vest4

0.60

MutPred

0.58

Gain of disorder (P = 0.0874);Gain of disorder (P = 0.0874);

MVP

0.74

MPC

0.37

ClinPred

0.40

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.070

gMVP

0.89

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