rs781476857

Variant names:

• chr5-149366111-C-T
• rs781476857
• NM_024028.4:c.640C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-149366111-C-T
• chr5-149366111-C-A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PP3_Strong

The NM_024028.4(PCYOX1L):​c.640C>T​(p.Arg214Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000322 in 1,613,764 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000031 (0 hom.)
• Consequence: PCYOX1L NM_024028.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.21
• Publications: 1 publications found

Genes affected

PCYOX1L (HGNC:28477): (prenylcysteine oxidase 1 like) Predicted to enable prenylcysteine oxidase activity. Predicted to be involved in prenylated protein catabolic process. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.963

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024028.4. 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
	PCYOX1L	NM_024028.4	MANE Select	c.640C>T	p.Arg214Trp	missense	Exon 4 of 6	NP_076933.3
	PCYOX1L	NM_001301054.2		c.589C>T	p.Arg197Trp	missense	Exon 4 of 6	NP_001287983.1
	PCYOX1L	NM_001301057.2		c.420-8C>T		splice_region intron	N/A	NP_001287986.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCYOX1L	ENST00000274569.9	TSL:2 MANE Select	c.640C>T	p.Arg214Trp	missense	Exon 4 of 6	ENSP00000274569.4	Q8NBM8-1
	PCYOX1L	ENST00000507621.1	TSL:1	n.3043C>T		non_coding_transcript_exon	Exon 1 of 3
	PCYOX1L	ENST00000511945.5	TSL:1	n.*407C>T		non_coding_transcript_exon	Exon 4 of 6	ENSP00000426091.1	Q8NBM8-2

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152226 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000282

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000799 AC: 20 AN: 250446 AF XY: 0.0000738

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000174

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000272

Gnomad FIN exome AF: 0.000233

Gnomad NFE exome AF: 0.0000265

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000315 AC: 46 AN: 1461420 Hom.: 0 Cov.: 31 AF XY: 0.0000344 AC XY: 25 AN XY: 727020

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.000112 AC: 5 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.000227 AC: 9 AN: 39700

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86244

European-Finnish (FIN) AF: 0.000151 AC: 8 AN: 53138

Middle Eastern (MID) AF: 0.000355 AC: 2 AN: 5634

European-Non Finnish (NFE) AF: 0.0000153 AC: 17 AN: 1111994

Other (OTH) AF: 0.0000331 AC: 2 AN: 60380

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152344 Hom.: 0 Cov.: 33 AF XY: 0.0000671 AC XY: 5 AN XY: 74498

African (AFR) AF: 0.00 AC: 0 AN: 41582

American (AMR) AF: 0.000196 AC: 3 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.000282 AC: 3 AN: 10624

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.0000508 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.0000494 AC: 6

ClinVar

ClinVar submissions

Significance: Uncertain significance

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	0.25
BayesDel_addAF	Benign	-0.0028	T
BayesDel_noAF	Uncertain	0.060
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T
Eigen	Uncertain	0.26
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.067	D
MetaRNN	Pathogenic	0.96	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		1.2
PrimateAI	Uncertain	0.73	T
PROVEAN	Pathogenic	-5.9	D
REVEL	Uncertain	0.60
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0070	D
Polyphen		1.0	D
Vest4		0.97
MutPred		0.86		Loss of disorder (P = 0.0458)
MVP		0.31
MPC		0.72
ClinPred		0.72	D
GERP RS		3.3
Varity_R		0.80
gMVP		0.88
Mutation Taster		=55/45	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: rs781476857; hg19: chr5-148745674; COSMIC: COSV108039822; COSMIC: COSV108039822;