NM_152911.4:c.157C>T

Variant names:

• chr10-133379473-C-T
• rs1035808162
• NM_152911.4:c.157C>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_152911.4(PAOX):​c.157C>T​(p.Arg53Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000163 in 1,225,530 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 30)
  • Exomes 𝑓: 9.3e-7 (0 hom.)
• Consequence: PAOX NM_152911.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.862
• 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.914

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.157C>T	p.Arg53Cys	missense	Exon 1 of 7	NP_690875.1	Q6QHF9-2
	PAOX	NM_207128.3		c.157C>T	p.Arg53Cys	missense	Exon 1 of 6	NP_997011.1	Q6QHF9-4
	PAOX	NM_207127.3		c.157C>T	p.Arg53Cys	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.157C>T	p.Arg53Cys	missense	Exon 1 of 7	ENSP00000278060.5	Q6QHF9-2
	PAOX	ENST00000357296.7	TSL:1	c.157C>T	p.Arg53Cys	missense	Exon 1 of 6	ENSP00000349847.3	Q6QHF9-4
	PAOX	ENST00000480071.2	TSL:1	c.157C>T	p.Arg53Cys	missense	Exon 1 of 5	ENSP00000435514.1	Q6QHF9-5

Frequencies

GnomAD3 genomes AF: 0.00000659 AC: 1 AN: 151694 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 9.31e-7 AC: 1 AN: 1073836 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 507052

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

African (AFR) AF: 0.00 AC: 0 AN: 22642

American (AMR) AF: 0.00 AC: 0 AN: 8208

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14066

East Asian (EAS) AF: 0.00 AC: 0 AN: 26156

South Asian (SAS) AF: 0.00 AC: 0 AN: 19424

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21038

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2894

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 916212

Other (OTH) AF: 0.0000232 AC: 1 AN: 43196

⚠️ 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 AF: 0.00000659 AC: 1 AN: 151694 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 74068

African (AFR) AF: 0.0000242 AC: 1 AN: 41358

American (AMR) AF: 0.00 AC: 0 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5024

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10582

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67870

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	Pathogenic	0.85
BayesDel_addAF	Pathogenic	0.43	D
BayesDel_noAF	Pathogenic	0.38
CADD	Pathogenic	33
DANN	Uncertain	1.0
Eigen	Uncertain	0.67
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Benign	0.34	N
LIST_S2	Uncertain	0.97	D
M_CAP	Pathogenic	0.98	D
MetaRNN	Pathogenic	0.91	D
MetaSVM	Pathogenic	1.1	D
MutationAssessor	Uncertain	2.4	M
PhyloP100		0.86
PrimateAI	Pathogenic	0.94	D
PROVEAN	Pathogenic	-6.5	D
REVEL	Pathogenic	0.82
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.52
MutPred		0.74		Loss of MoRF binding (P = 0.0051)
MVP		0.96
MPC		0.88
ClinPred		1.0	D
GERP RS		4.2
PromoterAI		-0.17	Neutral
gMVP		0.92
Mutation Taster		=25/75	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs1035808162; hg19: chr10-135192977;