chr5-149358079-C-G

Variant names:

• chr5-149358079-C-G
• rs945320462
• NM_024028.4:c.11C>G

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.11C>G​(p.Ala4Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000794 in 1,259,526 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. A4V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.9e-7 (0 hom.)
• Consequence: PCYOX1L NM_024028.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.23
• 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=0.0641053).

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.11C>G	p.Ala4Gly	missense	Exon 1 of 6	NP_076933.3
	PCYOX1L	NM_001301054.2		c.-57C>G		5_prime_UTR	Exon 1 of 6	NP_001287983.1
	PCYOX1L	NM_001301057.2		c.-57C>G		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.11C>G	p.Ala4Gly	missense	Exon 1 of 6	ENSP00000274569.4	Q8NBM8-1
	PCYOX1L	ENST00000505669.5	TSL:1	n.11C>G		non_coding_transcript_exon	Exon 1 of 6	ENSP00000427166.1	Q8NBM8-2
	PCYOX1L	ENST00000511945.5	TSL:1	n.11C>G		non_coding_transcript_exon	Exon 1 of 6	ENSP00000426091.1	Q8NBM8-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.94e-7 AC: 1 AN: 1259526 Hom.: 0 Cov.: 29 AF XY: 0.00000162 AC XY: 1 AN XY: 618124

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000392 AC: 1 AN: 25512

American (AMR) AF: 0.00 AC: 0 AN: 20686

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20402

East Asian (EAS) AF: 0.00 AC: 0 AN: 27272

South Asian (SAS) AF: 0.00 AC: 0 AN: 62568

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31258

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3656

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1016402

Other (OTH) AF: 0.00 AC: 0 AN: 51770

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	13
DANN	Benign	0.72
DEOGEN2	Benign	0.00034	T
Eigen	Benign	-0.92
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.44	T
M_CAP	Uncertain	0.086	D
MetaRNN	Benign	0.064	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.2
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-0.060	N
REVEL	Benign	0.030
Sift	Benign	0.24	T
Sift4G	Uncertain	0.023	D
Polyphen		0.0	B
Vest4		0.17
MutPred		0.24		Loss of helix (P = 0.0076)
MVP		0.13
MPC		0.18
ClinPred		0.039	T
GERP RS		3.4
PromoterAI		0.021	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.034
gMVP		0.30
Mutation Taster		=86/14	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: rs945320462; hg19: chr5-148737642;