5-149358117-G-T

Variant names:

• chr5-149358117-G-T
• rs756755916
• NM_024028.4:c.49G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_024028.4(PCYOX1L):​c.49G>T​(p.Ala17Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000275 in 1,454,790 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A17T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000023 (0 hom.)
• Consequence: PCYOX1L NM_024028.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.811
• Publications: 0 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]

GRPEL2-AS1 (HGNC:48999): (GRPEL2 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.062442392).

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.49G>T	p.Ala17Ser	missense	Exon 1 of 6	NP_076933.3
	PCYOX1L	NM_001301054.2		c.-19G>T		5_prime_UTR	Exon 1 of 6	NP_001287983.1
	PCYOX1L	NM_001301057.2		c.-19G>T		5_prime_UTR	Exon 1 of 6	NP_001287986.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCYOX1L	ENST00000274569.9	TSL:2 MANE Select	c.49G>T	p.Ala17Ser	missense	Exon 1 of 6	ENSP00000274569.4	Q8NBM8-1
	PCYOX1L	ENST00000505669.5	TSL:1	n.49G>T		non_coding_transcript_exon	Exon 1 of 6	ENSP00000427166.1	Q8NBM8-2
	PCYOX1L	ENST00000511945.5	TSL:1	n.49G>T		non_coding_transcript_exon	Exon 1 of 6	ENSP00000426091.1	Q8NBM8-2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152130 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000230 AC: 3 AN: 1302660 Hom.: 0 Cov.: 32 AF XY: 0.00000156 AC XY: 1 AN XY: 641192

African (AFR) AF: 0.00 AC: 0 AN: 26700

American (AMR) AF: 0.00 AC: 0 AN: 25378

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22954

East Asian (EAS) AF: 0.00 AC: 0 AN: 27842

South Asian (SAS) AF: 0.00 AC: 0 AN: 70294

European-Finnish (FIN) AF: 0.0000299 AC: 1 AN: 33446

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3834

European-Non Finnish (NFE) AF: 9.63e-7 AC: 1 AN: 1038376

Other (OTH) AF: 0.0000186 AC: 1 AN: 53836

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152130 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74326

African (AFR) AF: 0.00 AC: 0 AN: 41444

American (AMR) AF: 0.00 AC: 0 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67990

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	14
DANN	Benign	0.95
DEOGEN2	Benign	0.0024	T
Eigen	Benign	-0.87
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.062	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.81
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	0.090	N
REVEL	Benign	0.046
Sift	Benign	0.88	T
Sift4G	Benign	0.94	T
Polyphen		0.0030	B
Vest4		0.26
MutPred		0.40		Gain of glycosylation at A17 (P = 0.0041)
MVP		0.081
MPC		0.17
ClinPred		0.088	T
GERP RS		3.1
PromoterAI		-0.036	Neutral
Varity_R		0.038
gMVP		0.11
Mutation Taster		=95/5	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: rs756755916; hg19: chr5-148737680;