rs2706762

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 36 publications found

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

Our verdict: Benign. The variant received -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

GnomAD2 exomes AF: 0.0985 AC: 24775 AN: 251428 AF XY: 0.103

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 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

African (AFR) AF: 0.0204 AC: 683 AN: 33448

American (AMR) AF: 0.0569 AC: 2544 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 4051 AN: 26106

East Asian (EAS) AF: 0.000252 AC: 10 AN: 39684

South Asian (SAS) AF: 0.0860 AC: 7413 AN: 86202

European-Finnish (FIN) AF: 0.0678 AC: 3622 AN: 53416

Middle Eastern (MID) AF: 0.126 AC: 728 AN: 5766

European-Non Finnish (NFE) AF: 0.149 AC: 164972 AN: 1109148

Other (OTH) AF: 0.118 AC: 7127 AN: 60306

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

African (AFR) AF: 0.0251 AC: 1042 AN: 41544

American (AMR) AF: 0.0748 AC: 1144 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 539 AN: 3470

East Asian (EAS) AF: 0.000771 AC: 4 AN: 5188

South Asian (SAS) AF: 0.0805 AC: 388 AN: 4820

European-Finnish (FIN) AF: 0.0626 AC: 664 AN: 10600

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.150 AC: 10211 AN: 68004

Other (OTH) AF: 0.0957 AC: 202 AN: 2110

Alfa AF: 0.131 Hom.: 4892

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;.;.
PhyloP100		3.1
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
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2706762; hg19: chr2-70488470; COSMIC: COSV104580485;