NM_016297.4:c.32C>A

Variant names:

• chr2-70258196-C-A
• rs779530395
• NM_016297.4:c.32C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_016297.4(PCYOX1):​c.32C>A​(p.Ser11*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000691 in 1,446,442 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: PCYOX1 NM_016297.4 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.341
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016297.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCYOX1	NM_016297.4	MANE Select	c.32C>A	p.Ser11*	stop_gained	Exon 1 of 6	NP_057381.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCYOX1	ENST00000433351.7	TSL:1 MANE Select	c.32C>A	p.Ser11*	stop_gained	Exon 1 of 6	ENSP00000387654.2	Q9UHG3-1
	PCYOX1	ENST00000884434.1		c.32C>A	p.Ser11*	stop_gained	Exon 1 of 7	ENSP00000554493.1
	PCYOX1	ENST00000955833.1		c.32C>A	p.Ser11*	stop_gained	Exon 1 of 6	ENSP00000625892.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 229566 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS 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: 6.91e-7 AC: 1 AN: 1446442 Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1 AN XY: 720176

African (AFR) AF: 0.00 AC: 0 AN: 31748

American (AMR) AF: 0.00 AC: 0 AN: 44286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25766

East Asian (EAS) AF: 0.00 AC: 0 AN: 38626

South Asian (SAS) AF: 0.00 AC: 0 AN: 85780

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46972

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4984

European-Non Finnish (NFE) AF: 9.02e-7 AC: 1 AN: 1108470

Other (OTH) AF: 0.00 AC: 0 AN: 59810

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.14
CADD	Pathogenic	33
DANN	Uncertain	0.98
Eigen	Benign	0.14
Eigen_PC	Benign	-0.20
FATHMM_MKL	Benign	0.067	N
PhyloP100		-0.34
Vest4		0.10
GERP RS		2.8
PromoterAI		-0.15	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=33/167	disease causing (fs/PTC)

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: rs779530395; hg19: chr2-70485328;