2-70258219-C-T

Variant names:

• chr2-70258219-C-T
• rs374420773
• NM_016297.4:c.55C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_016297.4(PCYOX1):​c.55C>T​(p.Leu19Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000692 in 1,445,918 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign 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 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0140
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP7: Synonymous conserved (PhyloP=0.014 with no splicing effect.

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.55C>T	p.Leu19Leu	synonymous	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.55C>T	p.Leu19Leu	synonymous	Exon 1 of 6	ENSP00000387654.2	Q9UHG3-1
	PCYOX1	ENST00000884434.1		c.55C>T	p.Leu19Leu	synonymous	Exon 1 of 7	ENSP00000554493.1
	PCYOX1	ENST00000955833.1		c.55C>T	p.Leu19Leu	synonymous	Exon 1 of 6	ENSP00000625892.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.92e-7 AC: 1 AN: 1445918 Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1 AN XY: 719876

African (AFR) AF: 0.00 AC: 0 AN: 31802

American (AMR) AF: 0.00 AC: 0 AN: 44210

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25772

East Asian (EAS) AF: 0.00 AC: 0 AN: 38586

South Asian (SAS) AF: 0.00 AC: 0 AN: 85722

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46928

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4790

European-Non Finnish (NFE) AF: 9.02e-7 AC: 1 AN: 1108388

Other (OTH) AF: 0.00 AC: 0 AN: 59720

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	8.3
DANN	Benign	0.81
PhyloP100		0.014
PromoterAI		0.11	Neutral
Mutation Taster		=100/0	polymorphism

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: rs374420773; hg19: chr2-70485351;