chr10-133380374-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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. 13/19 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

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 1 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAOX	NM_152911.4	c.557C>T	p.Ser186Phe	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.557C>T	p.Ser186Phe	missense_variant	Exon 2 of 7	1	NM_152911.4	ENSP00000278060.5
ENSG00000254536	ENST00000468317.3	n.170C>T		non_coding_transcript_exon_variant	Exon 1 of 16	5		ENSP00000436767.2
ENSG00000254536	ENST00000670407.1	n.170C>T		non_coding_transcript_exon_variant	Exon 1 of 7			ENSP00000499264.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 06, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.557C>T (p.S186F) 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 557, causing the serine (S) at amino acid position 186 to be replaced by a phenylalanine (F). 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	0.33
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;T;T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.30	T;T;T
MetaSVM	Benign	-0.39	T
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-2.2	N;N;D
REVEL	Benign	0.26
Sift	Benign	0.18	T;T;T
Sift4G	Benign	0.71	T;T;T
Polyphen		0.71	P;B;P
Vest4		0.17
MutPred		0.73		Loss of helix (P = 0.0626);Loss of helix (P = 0.0626);Loss of helix (P = 0.0626);
MVP		0.53
MPC		0.37
ClinPred		0.15	T
GERP RS		-1.5
gMVP		0.47

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-135193878;