rs1849322345

Variant names:

• chr10-133380209-C-G
• rs1849322345
• NM_152911.4:c.392C>G

Your query was ambiguous. Multiple possible variants found:

• chr10-133380209-C-G
• chr10-133380209-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152911.4(PAOX):​c.392C>G​(p.Ala131Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,330 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PAOX NM_152911.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.224
• 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]

ENSG00000254536 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13460502).

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.392C>G	p.Ala131Gly	missense	Exon 2 of 7	NP_690875.1	Q6QHF9-2
	PAOX	NM_207128.3		c.392C>G	p.Ala131Gly	missense	Exon 2 of 6	NP_997011.1	Q6QHF9-4
	PAOX	NM_207127.3		c.392C>G	p.Ala131Gly	missense	Exon 2 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.392C>G	p.Ala131Gly	missense	Exon 2 of 7	ENSP00000278060.5	Q6QHF9-2
	PAOX	ENST00000357296.7	TSL:1	c.392C>G	p.Ala131Gly	missense	Exon 2 of 6	ENSP00000349847.3	Q6QHF9-4
	PAOX	ENST00000480071.2	TSL:1	c.392C>G	p.Ala131Gly	missense	Exon 2 of 5	ENSP00000435514.1	Q6QHF9-5

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460330 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726440

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52126

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111838

Other (OTH) AF: 0.00 AC: 0 AN: 60342

GnomAD4 genome Cov.: 34

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.076	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	11
DANN	Benign	0.96
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.68	T
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.40	T
MutationAssessor	Benign	1.5	L
PhyloP100		-0.22
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.19
Sift	Benign	0.28	T
Sift4G	Benign	0.38	T
Polyphen		0.031	B
Vest4		0.14
MutPred		0.59		Loss of stability (P = 0.1381)
MVP		0.69
MPC		0.20
ClinPred		0.093	T
GERP RS		1.9
gMVP		0.40
Mutation Taster		=91/9	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: rs1849322345; hg19: chr10-135193713;