chr5-149358088-T-A

Variant names:

• chr5-149358088-T-A
• NM_024028.4:c.20T>A

Variant summary

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

The NM_024028.4(PCYOX1L):​c.20T>A​(p.Leu7Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000778 in 1,284,640 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.8e-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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCYOX1L	NM_024028.4	c.20T>A	p.Leu7Gln	missense_variant	Exon 1 of 6	ENST00000274569.9	NP_076933.3
PCYOX1L	NM_001301054.2	c.-48T>A		5_prime_UTR_variant	Exon 1 of 6		NP_001287983.1
PCYOX1L	NM_001301057.2	c.-48T>A		5_prime_UTR_variant	Exon 1 of 6		NP_001287986.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCYOX1L	ENST00000274569.9	c.20T>A	p.Leu7Gln	missense_variant	Exon 1 of 6	2	NM_024028.4	ENSP00000274569.4
PCYOX1L	ENST00000505669.5	n.20T>A		non_coding_transcript_exon_variant	Exon 1 of 6	1		ENSP00000427166.1
PCYOX1L	ENST00000511945.5	n.20T>A		non_coding_transcript_exon_variant	Exon 1 of 6	1		ENSP00000426091.1
PCYOX1L	ENST00000510990.6	n.20T>A		non_coding_transcript_exon_variant	Exon 1 of 5	4		ENSP00000422063.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.78e-7 AC: 1 AN: 1284640 Hom.: 0 Cov.: 31 AF XY: 0.00000158 AC XY: 1 AN XY: 631976

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: 9.72e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 20, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.20T>A (p.L7Q) alteration is located in exon 1 (coding exon 1) of the PCYOX1L gene. This alteration results from a T to A substitution at nucleotide position 20, causing the leucine (L) at amino acid position 7 to be replaced by a glutamine (Q). 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	0.18
BayesDel_addAF	Uncertain	0.014	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	21
DANN	Benign	0.74
DEOGEN2	Benign	0.0031	T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.083	D
MetaRNN	Uncertain	0.47	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.25
Sift	Benign	0.030	D
Sift4G	Uncertain	0.032	D
Polyphen		0.88	P
Vest4		0.58
MutPred		0.33		Gain of disorder (P = 0.0546);
MVP		0.10
MPC		0.19
ClinPred		0.25	T
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.25
gMVP		0.74

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: chr5-148737651;