chr10-133380374-C-T

Variant names:

• chr10-133380374-C-T
• NM_152911.4:c.557C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_152911.4(PAOX):​c.557C>T​(p.Ser186Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: PAOX NM_152911.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.963
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29580498).

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.557C>T	p.Ser186Phe	missense	Exon 2 of 7	NP_690875.1	Q6QHF9-2
	PAOX	NM_207128.3		c.557C>T	p.Ser186Phe	missense	Exon 2 of 6	NP_997011.1	Q6QHF9-4
	PAOX	NM_207127.3		c.557C>T	p.Ser186Phe	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.557C>T	p.Ser186Phe	missense	Exon 2 of 7	ENSP00000278060.5	Q6QHF9-2
	PAOX	ENST00000357296.7	TSL:1	c.557C>T	p.Ser186Phe	missense	Exon 2 of 6	ENSP00000349847.3	Q6QHF9-4
	PAOX	ENST00000480071.2	TSL:1	c.557C>T	p.Ser186Phe	missense	Exon 2 of 5	ENSP00000435514.1	Q6QHF9-5

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 31

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	0.33
BayesDel_addAF	Benign	-0.011	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	13
DANN	Benign	0.82
Eigen	Benign	-0.91
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.055	N
LIST_S2	Benign	0.84	T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-0.39	T
PhyloP100		-0.96
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.26
Sift	Benign	0.18	T
Sift4G	Benign	0.71	T
Polyphen		0.71	P
Vest4		0.17
MutPred		0.73		Loss of helix (P = 0.0626)
MVP		0.53
MPC		0.37
ClinPred		0.15	T
GERP RS		-1.5
gMVP		0.47
Mutation Taster		=90/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

hg19: chr10-135193878;