2-70275150-C-T

Variant names:

• chr2-70275150-C-T
• rs199918295
• NM_016297.4:c.686C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_016297.4(PCYOX1):​c.686C>T​(p.Thr229Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000954 in 1,613,572 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000092 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000096 (2 hom.)
• Consequence: PCYOX1 NM_016297.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.360
• Publications: 1 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.011731178).
• BP6: Variant 2-70275150-C-T is Benign according to our data. Variant chr2-70275150-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2230338.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

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.686C>T	p.Thr229Met	missense	Exon 4 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.686C>T	p.Thr229Met	missense	Exon 4 of 6	ENSP00000387654.2	Q9UHG3-1
	PCYOX1	ENST00000884434.1		c.797C>T	p.Thr266Met	missense	Exon 5 of 7	ENSP00000554493.1
	PCYOX1	ENST00000955833.1		c.686C>T	p.Thr229Met	missense	Exon 4 of 6	ENSP00000625892.1

Frequencies

GnomAD3 genomes AF: 0.0000920 AC: 14 AN: 152170 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000171 AC: 43 AN: 251486 AF XY: 0.000191

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000397

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000440

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000958 AC: 140 AN: 1461284 Hom.: 2 Cov.: 30 AF XY: 0.000117 AC XY: 85 AN XY: 726984

African (AFR) AF: 0.00 AC: 0 AN: 33464

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000497 AC: 13 AN: 26136

East Asian (EAS) AF: 0.000151 AC: 6 AN: 39700

South Asian (SAS) AF: 0.000823 AC: 71 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000360 AC: 40 AN: 1111440

Other (OTH) AF: 0.000166 AC: 10 AN: 60386

GnomAD4 genome AF: 0.0000919 AC: 14 AN: 152288 Hom.: 0 Cov.: 31 AF XY: 0.000107 AC XY: 8 AN XY: 74464

African (AFR) AF: 0.0000241 AC: 1 AN: 41564

American (AMR) AF: 0.00 AC: 0 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.000577 AC: 2 AN: 3468

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5186

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68022

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.000156 Hom.: 0

Bravo AF: 0.0000945

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000255 AC: 31

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	9.9
DANN	Benign	0.85
DEOGEN2	Benign	0.015	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.012	N
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.012	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.40	N
PhyloP100		0.36
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.041
Sift	Benign	0.15	T
Sift4G	Benign	0.15	T
Polyphen		0.062	B
Vest4		0.18
MVP		0.17
MPC		0.092
ClinPred		0.0076	T
GERP RS		-2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.022
gMVP		0.66
Mutation Taster		=96/4	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: rs199918295; hg19: chr2-70502282;