10-133379480-G-T

Variant names:

• chr10-133379480-G-T
• rs770874285
• NM_152911.4:c.164G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_152911.4(PAOX):​c.164G>T​(p.Arg55Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000931 in 1,073,778 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. R55C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 9.3e-7 (0 hom.)
• Consequence: PAOX NM_152911.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.28
• Publications: 0 publications found

Genes affected

PAOX (HGNC:20837): (polyamine oxidase) Enables polyamine oxidase activity. Involved in polyamine metabolic process and positive regulation of spermidine biosynthetic process. Predicted to be located in cytosol and peroxisomal matrix. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.4091853).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152911.4. 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
	PAOX	NM_152911.4	MANE Select	c.164G>T	p.Arg55Leu	missense	Exon 1 of 7	NP_690875.1	Q6QHF9-2
	PAOX	NM_207128.3		c.164G>T	p.Arg55Leu	missense	Exon 1 of 6	NP_997011.1	Q6QHF9-4
	PAOX	NM_207127.3		c.164G>T	p.Arg55Leu	missense	Exon 1 of 5	NP_997010.1	Q6QHF9-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAOX	ENST00000278060.10	TSL:1 MANE Select	c.164G>T	p.Arg55Leu	missense	Exon 1 of 7	ENSP00000278060.5	Q6QHF9-2
	PAOX	ENST00000357296.7	TSL:1	c.164G>T	p.Arg55Leu	missense	Exon 1 of 6	ENSP00000349847.3	Q6QHF9-4
	PAOX	ENST00000480071.2	TSL:1	c.164G>T	p.Arg55Leu	missense	Exon 1 of 5	ENSP00000435514.1	Q6QHF9-5

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 9.31e-7 AC: 1 AN: 1073778 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 507016

African (AFR) AF: 0.00 AC: 0 AN: 22632

American (AMR) AF: 0.00 AC: 0 AN: 8206

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14058

East Asian (EAS) AF: 0.0000382 AC: 1 AN: 26156

South Asian (SAS) AF: 0.00 AC: 0 AN: 19414

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21028

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2896

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 916186

Other (OTH) AF: 0.00 AC: 0 AN: 43202

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Uncertain	24
DANN	Uncertain	1.0
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.13
FATHMM_MKL	Benign	0.29	N
LIST_S2	Uncertain	0.91	D
M_CAP	Pathogenic	0.93	D
MetaRNN	Benign	0.41	T
MetaSVM	Uncertain	-0.056	T
MutationAssessor	Benign	0.030	N
PhyloP100		2.3
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-1.8	N
REVEL	Uncertain	0.54
Sift	Benign	0.20	T
Sift4G	Benign	0.57	T
Polyphen		0.12	B
Vest4		0.37
MutPred		0.71		Loss of MoRF binding (P = 0.0309)
MVP		0.88
MPC		0.41
ClinPred		0.60	D
GERP RS		3.3
PromoterAI		-0.14	Neutral
gMVP		0.60
Mutation Taster		=75/25	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs770874285; hg19: chr10-135192984;