2-70258243-G-C

Position:

• chr2-70258243-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016297.4(PCYOX1):​c.79G>C​(p.Gly27Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: PCYOX1 NM_016297.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.151

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 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=0.09855351).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCYOX1	NM_016297.4	c.79G>C	p.Gly27Arg	missense_variant	1/6	ENST00000433351.7	NP_057381.3
PCYOX1	XM_047444689.1	c.-120+308G>C		intron_variant			XP_047300645.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCYOX1	ENST00000433351.7	c.79G>C	p.Gly27Arg	missense_variant	1/6	1	NM_016297.4	ENSP00000387654.2
PCYOX1	ENST00000264441.9	c.79G>C	p.Gly27Arg	missense_variant	1/6	5		ENSP00000264441.5
PCYOX1	ENST00000414812.5	c.-120+308G>C		intron_variant		3		ENSP00000413178.1
PCYOX1	ENST00000422380.5	c.-120+810G>C		intron_variant		4		ENSP00000404327.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 28, 2024

The c.79G>C (p.G27R) alteration is located in exon 1 (coding exon 1) of the PCYOX1 gene. This alteration results from a G to C substitution at nucleotide position 79, causing the glycine (G) at amino acid position 27 to be replaced by an arginine (R). 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	0.096
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	16
DANN	Benign	0.66
DEOGEN2	Benign	0.030	T;.
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.52	T;T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.099	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.69	N;.
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	0.17	N;N
REVEL	Benign	0.039
Sift	Benign	0.22	T;T
Sift4G	Benign	0.59	T;T
Polyphen		0.0010	B;.
Vest4		0.17
MutPred		0.47		Gain of methylation at G27 (P = 0.0367);Gain of methylation at G27 (P = 0.0367);
MVP		0.42
MPC		0.095
ClinPred		0.19	T
GERP RS		2.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.030
gMVP		0.64

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-70485375;