10-133380149-C-T

Variant names:

• chr10-133380149-C-T
• rs1350871221
• NM_152911.4:c.332C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152911.4(PAOX):​c.332C>T​(p.Pro111Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000345 in 1,449,130 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 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: 0.0000035 (0 hom.)
• Consequence: PAOX NM_152911.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.72

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25139767).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAOX	NM_152911.4	c.332C>T	p.Pro111Leu	missense_variant	Exon 2 of 7	ENST00000278060.10	NP_690875.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAOX	ENST00000278060.10	c.332C>T	p.Pro111Leu	missense_variant	Exon 2 of 7	1	NM_152911.4	ENSP00000278060.5
ENSG00000254536	ENST00000468317.3	n.-56C>T		non_coding_transcript_exon_variant	Exon 1 of 16	5		ENSP00000436767.2
ENSG00000254536	ENST00000670407.1	n.-56C>T		non_coding_transcript_exon_variant	Exon 1 of 7			ENSP00000499264.1
ENSG00000254536	ENST00000468317.3	n.-56C>T		5_prime_UTR_variant	Exon 1 of 16	5		ENSP00000436767.2
ENSG00000254536	ENST00000670407.1	n.-56C>T		5_prime_UTR_variant	Exon 1 of 7			ENSP00000499264.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD3 exomes AF: 0.0000166 AC: 4 AN: 240908 Hom.: 0 AF XY: 0.0000229 AC XY: 3 AN XY: 130824

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000885

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000925

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000345 AC: 5 AN: 1449130 Hom.: 0 Cov.: 31 AF XY: 0.00000417 AC XY: 3 AN XY: 719360

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000681

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000181

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 23, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.332C>T (p.P111L) alteration is located in exon 2 (coding exon 2) of the PAOX gene. This alteration results from a C to T substitution at nucleotide position 332, causing the proline (P) at amino acid position 111 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	18
DANN	Benign	0.88
Eigen	Benign	-0.091
Eigen_PC	Benign	-0.012
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Uncertain	0.89	D;D;D
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.25	T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.8	M;M;M
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-2.8	D;D;D
REVEL	Benign	0.11
Sift	Benign	0.50	T;T;T
Sift4G	Benign	0.63	T;T;T
Polyphen		0.65	P;P;P
Vest4		0.56
MutPred		0.55		Loss of disorder (P = 0.0289);Loss of disorder (P = 0.0289);Loss of disorder (P = 0.0289);
MVP		0.41
MPC		0.61
ClinPred		0.91	D
GERP RS		4.0
gMVP		0.65

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

Publications

LitVar

Other links and lift over

dbSNP: rs1350871221; hg19: chr10-135193653;