5-149358096-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024028.4(PCYOX1L):c.28G>C(p.Ala10Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000154 in 1,295,166 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: PCYOX1L NM_024028.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.389

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.069395274).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCYOX1L	NM_024028.4	c.28G>C	p.Ala10Pro	missense_variant	1/6	ENST00000274569.9
PCYOX1L	NM_001301054.2	c.-40G>C		5_prime_UTR_variant	1/6
PCYOX1L	NM_001301057.2	c.-40G>C		5_prime_UTR_variant	1/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCYOX1L	ENST00000274569.9	c.28G>C	p.Ala10Pro	missense_variant	1/6	2	NM_024028.4	P1
PCYOX1L	ENST00000505669.5	c.28G>C	p.Ala10Pro	missense_variant, NMD_transcript_variant	1/6	1
PCYOX1L	ENST00000511945.5	c.28G>C	p.Ala10Pro	missense_variant, NMD_transcript_variant	1/6	1
PCYOX1L	ENST00000510990.6	c.28G>C	p.Ala10Pro	missense_variant, NMD_transcript_variant	1/5	4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000154 AC: 2 AN: 1295166 Hom.: 0 Cov.: 31 AF XY: 0.00000157 AC XY: 1 AN XY: 637418

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000193

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 28, 2023

The c.28G>C (p.A10P) alteration is located in exon 1 (coding exon 1) of the PCYOX1L gene. This alteration results from a G to C substitution at nucleotide position 28, causing the alanine (A) at amino acid position 10 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
Cadd	Benign	13
Dann	Benign	0.76
DEOGEN2	Benign	0.00096	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.069	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.0	N
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-0.34	N
REVEL	Benign	0.17
Sift	Benign	0.26	T
Sift4G	Benign	0.21	T
Polyphen		0.052	B
Vest4		0.27
MutPred		0.40		Gain of loop (P = 0.0051);
MVP		0.12
MPC		0.24
ClinPred		0.072	T
GERP RS		0.70
Varity_R		0.12
gMVP		0.56

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-148737659;