10-133380200-C-T

Variant names:

• chr10-133380200-C-T
• rs753690252
• NM_152911.4:c.383C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_152911.4(PAOX):​c.383C>T​(p.Ala128Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000143 in 1,612,390 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 34)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: PAOX NM_152911.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.270
• Publications: 1 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: 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=0.067563444).

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.383C>T	p.Ala128Val	missense	Exon 2 of 7	NP_690875.1	Q6QHF9-2
	PAOX	NM_207128.3		c.383C>T	p.Ala128Val	missense	Exon 2 of 6	NP_997011.1	Q6QHF9-4
	PAOX	NM_207127.3		c.383C>T	p.Ala128Val	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.383C>T	p.Ala128Val	missense	Exon 2 of 7	ENSP00000278060.5	Q6QHF9-2
	PAOX	ENST00000357296.7	TSL:1	c.383C>T	p.Ala128Val	missense	Exon 2 of 6	ENSP00000349847.3	Q6QHF9-4
	PAOX	ENST00000480071.2	TSL:1	c.383C>T	p.Ala128Val	missense	Exon 2 of 5	ENSP00000435514.1	Q6QHF9-5

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152198 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

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

GnomAD2 exomes AF: 0.0000161 AC: 4 AN: 248876 AF XY: 0.0000148

Gnomad AFR exome AF: 0.000125

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000545

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000116 AC: 17 AN: 1460192 Hom.: 0 Cov.: 31 AF XY: 0.0000151 AC XY: 11 AN XY: 726336

African (AFR) AF: 0.0000597 AC: 2 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26112

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39696

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52138

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111704

Other (OTH) AF: 0.000166 AC: 10 AN: 60354

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152198 Hom.: 0 Cov.: 34 AF XY: 0.0000269 AC XY: 2 AN XY: 74362

African (AFR) AF: 0.000121 AC: 5 AN: 41456

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000329 Hom.: 0

Bravo AF: 0.0000416

ExAC AF: 0.00000825 AC: 1

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	0.10
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	14
DANN	Benign	0.89
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.054	N
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.075	D
MetaRNN	Benign	0.068	T
MetaSVM	Benign	-0.42	T
MutationAssessor	Benign	0.41	N
PhyloP100		-0.27
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.72	N
REVEL	Benign	0.19
Sift	Benign	0.14	T
Sift4G	Benign	0.29	T
Polyphen		0.0030	B
Vest4		0.12
MVP		0.69
MPC		0.19
ClinPred		0.028	T
GERP RS		0.88
gMVP		0.36
Mutation Taster		=94/6	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: rs753690252; hg19: chr10-135193704; COSMIC: COSV53373969;