chr10-133379479-C-T

Variant names:

• chr10-133379479-C-T
• rs944947936
• NM_152911.4:c.163C>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_152911.4(PAOX):​c.163C>T​(p.Arg55Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,073,838 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R55H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 0.000013 (0 hom.)
• Consequence: PAOX NM_152911.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.498

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]

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=0.40609473).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAOX	NM_152911.4	c.163C>T	p.Arg55Cys	missense_variant	Exon 1 of 7	ENST00000278060.10	NP_690875.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAOX	ENST00000278060.10	c.163C>T	p.Arg55Cys	missense_variant	Exon 1 of 7	1	NM_152911.4	ENSP00000278060.5

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 0.0000130 AC: 14 AN: 1073838 Hom.: 0 Cov.: 31 AF XY: 0.00000592 AC XY: 3 AN XY: 507058

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: 0.0000153

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 29

Bravo AF: 0.0000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 07, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.163C>T (p.R55C) alteration is located in exon 1 (coding exon 1) of the PAOX gene. This alteration results from a C to T substitution at nucleotide position 163, causing the arginine (R) at amino acid position 55 to be replaced by a cysteine (C). 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	0.10
BayesDel_addAF	Uncertain	0.075	D
BayesDel_noAF	Benign	-0.13
CADD	Benign	23
DANN	Uncertain	1.0
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.040
FATHMM_MKL	Benign	0.66	D
LIST_S2	Uncertain	0.90	D;D;D
M_CAP	Pathogenic	0.94	D
MetaRNN	Benign	0.41	T;T;T
MetaSVM	Uncertain	-0.0019	T
MutationAssessor	Benign	1.4	L;L;L
PrimateAI	Pathogenic	0.91	D
PROVEAN	Uncertain	-2.5	D;D;D
REVEL	Uncertain	0.39
Sift	Benign	0.057	T;T;T
Sift4G	Benign	0.12	T;T;T
Polyphen		0.27	B;P;P
Vest4		0.20
MutPred		0.69		Loss of MoRF binding (P = 0.0088);Loss of MoRF binding (P = 0.0088);Loss of MoRF binding (P = 0.0088);
MVP		0.91
MPC		0.27
ClinPred		0.93	D
GERP RS		3.3
gMVP		0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: rs944947936; hg19: chr10-135192983;