10-133380209-C-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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. 14/20 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: 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

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=0.13460502).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAOX	NM_152911.4	c.392C>G	p.Ala131Gly	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.392C>G	p.Ala131Gly	missense_variant	Exon 2 of 7	1	NM_152911.4	ENSP00000278060.5
ENSG00000254536	ENST00000468317.3	n.5C>G		non_coding_transcript_exon_variant	Exon 1 of 16	5		ENSP00000436767.2
ENSG00000254536	ENST00000670407.1	n.5C>G		non_coding_transcript_exon_variant	Exon 1 of 7			ENSP00000499264.1

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 23, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.392C>G (p.A131G) alteration is located in exon 2 (coding exon 2) of the PAOX gene. This alteration results from a C to G substitution at nucleotide position 392, causing the alanine (A) at amino acid position 131 to be replaced by a glycine (G). 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	0.078
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;T;T
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.13	T;T;T
MetaSVM	Benign	-0.40	T
MutationAssessor	Benign	1.5	L;L;L
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.7	N;N;N
REVEL	Benign	0.19
Sift	Benign	0.28	T;T;T
Sift4G	Benign	0.38	T;T;T
Polyphen		0.031	B;B;B
Vest4		0.14
MutPred		0.59		Loss of stability (P = 0.1381);Loss of stability (P = 0.1381);Loss of stability (P = 0.1381);
MVP		0.69
MPC		0.20
ClinPred		0.093	T
GERP RS		1.9
gMVP		0.40

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-135193713;