5-149358152-A-T

Variant summary

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

The NM_024028.4(PCYOX1L):c.84A>T(p.Lys28Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000767 in 1,303,180 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 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: 7.7e-7 (0 hom.)
• Consequence: PCYOX1L NM_024028.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.20

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=0.21765977).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCYOX1L	NM_024028.4	c.84A>T	p.Lys28Asn	missense_variant	1/6	ENST00000274569.9
PCYOX1L	NM_001301054.2	c.17A>T	p.Lys6Ile	missense_variant	1/6
PCYOX1L	NM_001301057.2	c.17A>T	p.Lys6Ile	missense_variant	1/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCYOX1L	ENST00000274569.9	c.84A>T	p.Lys28Asn	missense_variant	1/6	2	NM_024028.4	P1
PCYOX1L	ENST00000505669.5	c.84A>T	p.Lys28Asn	missense_variant, NMD_transcript_variant	1/6	1
PCYOX1L	ENST00000511945.5	c.84A>T	p.Lys28Asn	missense_variant, NMD_transcript_variant	1/6	1
PCYOX1L	ENST00000510990.6	c.84A>T	p.Lys28Asn	missense_variant, NMD_transcript_variant	1/5	4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.0000127 AC: 1 AN: 78702 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 45132

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000460

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.67e-7 AC: 1 AN: 1303180 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 641918

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000358

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

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

Mar 05, 2024

The c.84A>T (p.K28N) alteration is located in exon 1 (coding exon 1) of the PCYOX1L gene. This alteration results from a A to T substitution at nucleotide position 84, causing the lysine (K) at amino acid position 28 to be replaced by an asparagine (N). 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	Pathogenic	0.67
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.53
Cadd	Benign	23
Dann	Benign	0.94
DEOGEN2	Benign	0.0029	T
Eigen	Benign	0.074
Eigen_PC	Benign	0.080
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.59	N
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.13
Sift	Benign	0.088	T
Sift4G	Uncertain	0.0090	D
Polyphen		1.0	D
Vest4		0.34
MutPred		0.51		Loss of methylation at K28 (P = 0.0098);
MVP		0.35
MPC		0.21
ClinPred		0.85	D
GERP RS		2.6
Varity_R		0.10
gMVP		0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1198809395; hg19: chr5-148737715;