rs2706762

Variant names:

• chr2-70261338-C-T
• rs2706762
• NM_016297.4:c.446C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016297.4(PCYOX1):​c.446C>T​(p.Ser149Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 1,611,022 control chromosomes in the GnomAD database, including 14,876 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.095 (903 hom., cov: 32)
  • Exomes 𝑓: 0.13 (13973 hom.)
• Consequence: PCYOX1 NM_016297.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.08

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0019338727).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCYOX1	NM_016297.4	c.446C>T	p.Ser149Phe	missense_variant	Exon 3 of 6	ENST00000433351.7	NP_057381.3
PCYOX1	XM_047444689.1	c.215C>T	p.Ser72Phe	missense_variant	Exon 3 of 6		XP_047300645.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCYOX1	ENST00000433351.7	c.446C>T	p.Ser149Phe	missense_variant	Exon 3 of 6	1	NM_016297.4	ENSP00000387654.2

Frequencies

GnomAD3 genomes AF: 0.0948 AC: 14415 AN: 152110 Hom.: 903 Cov.: 32

Gnomad AFR AF: 0.0252

Gnomad AMI AF: 0.191

Gnomad AMR AF: 0.0749

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.000769

Gnomad SAS AF: 0.0806

Gnomad FIN AF: 0.0626

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.0977

GnomAD3 exomes AF: 0.0985 AC: 24775 AN: 251428 Hom.: 1540 AF XY: 0.103 AC XY: 13937 AN XY: 135900

Gnomad AFR exome AF: 0.0229

Gnomad AMR exome AF: 0.0535

Gnomad ASJ exome AF: 0.155

Gnomad EAS exome AF: 0.000326

Gnomad SAS exome AF: 0.0826

Gnomad FIN exome AF: 0.0635

Gnomad NFE exome AF: 0.144

Gnomad OTH exome AF: 0.118

GnomAD4 exome AF: 0.131 AC: 191150 AN: 1458794 Hom.: 13973 Cov.: 29 AF XY: 0.131 AC XY: 94949 AN XY: 725930

Gnomad4 AFR exome AF: 0.0204

Gnomad4 AMR exome AF: 0.0569

Gnomad4 ASJ exome AF: 0.155

Gnomad4 EAS exome AF: 0.000252

Gnomad4 SAS exome AF: 0.0860

Gnomad4 FIN exome AF: 0.0678

Gnomad4 NFE exome AF: 0.149

Gnomad4 OTH exome AF: 0.118

GnomAD4 genome AF: 0.0946 AC: 14402 AN: 152228 Hom.: 903 Cov.: 32 AF XY: 0.0890 AC XY: 6624 AN XY: 74438

Gnomad4 AFR AF: 0.0251

Gnomad4 AMR AF: 0.0748

Gnomad4 ASJ AF: 0.155

Gnomad4 EAS AF: 0.000771

Gnomad4 SAS AF: 0.0805

Gnomad4 FIN AF: 0.0626

Gnomad4 NFE AF: 0.150

Gnomad4 OTH AF: 0.0957

Alfa AF: 0.138 Hom.: 3793

Bravo AF: 0.0918

TwinsUK AF: 0.142 AC: 526

ALSPAC AF: 0.147 AC: 568

ESP6500AA AF: 0.0313 AC: 138

ESP6500EA AF: 0.152 AC: 1309

ExAC AF: 0.0997 AC: 12103

Asia WGS AF: 0.0380 AC: 133 AN: 3478

EpiCase AF: 0.152

EpiControl AF: 0.153

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	18
DANN	Benign	0.16
DEOGEN2	Benign	0.0042	T;T;T;.;T
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.22
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.75	T;T;T;T;T
MetaRNN	Benign	0.0019	T;T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-0.53	.;.;N;.;.
PrimateAI	Benign	0.40	T
PROVEAN	Benign	2.2	N;N;N;N;N
REVEL	Benign	0.19
Sift	Benign	1.0	T;T;T;T;T
Sift4G	Benign	0.13	T;T;T;T;T
Polyphen		0.0	.;.;B;.;.
Vest4		0.049, 0.039
MPC		0.088
ClinPred		0.016	T
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.042
gMVP		0.79

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

Other links and lift over

dbSNP: rs2706762; hg19: chr2-70488470;