10-133380200-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_152911.4(PAOX):​c.383C>T​(p.Ala128Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000143 in 1,612,390 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 34)
Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

PAOX
NM_152911.4 missense

Scores

18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.270
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.067563444).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PAOXNM_152911.4 linkc.383C>T p.Ala128Val missense_variant Exon 2 of 7 ENST00000278060.10 NP_690875.1 Q6QHF9-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PAOXENST00000278060.10 linkc.383C>T p.Ala128Val missense_variant Exon 2 of 7 1 NM_152911.4 ENSP00000278060.5 Q6QHF9-2
ENSG00000254536ENST00000468317.3 linkn.-5C>T non_coding_transcript_exon_variant Exon 1 of 16 5 ENSP00000436767.2 B0QZA9
ENSG00000254536ENST00000670407.1 linkn.-5C>T non_coding_transcript_exon_variant Exon 1 of 7 ENSP00000499264.1 A0A590UJ37
ENSG00000254536ENST00000468317.3 linkn.-5C>T 5_prime_UTR_variant Exon 1 of 16 5 ENSP00000436767.2 B0QZA9
ENSG00000254536ENST00000670407.1 linkn.-5C>T 5_prime_UTR_variant Exon 1 of 7 ENSP00000499264.1 A0A590UJ37

Frequencies

GnomAD3 genomes
AF:
0.0000394
AC:
6
AN:
152198
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.000121
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000161
AC:
4
AN:
248876
Hom.:
0
AF XY:
0.0000148
AC XY:
2
AN XY:
135220
show subpopulations
Gnomad AFR exome
AF:
0.000125
Gnomad AMR exome
AF:
0.0000290
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000545
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000116
AC:
17
AN:
1460192
Hom.:
0
Cov.:
31
AF XY:
0.0000151
AC XY:
11
AN XY:
726336
show subpopulations
Gnomad4 AFR exome
AF:
0.0000597
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000756
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.00e-7
Gnomad4 OTH exome
AF:
0.000166
GnomAD4 genome
AF:
0.0000394
AC:
6
AN:
152198
Hom.:
0
Cov.:
34
AF XY:
0.0000269
AC XY:
2
AN XY:
74362
show subpopulations
Gnomad4 AFR
AF:
0.000121
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000329
Hom.:
0
Bravo
AF:
0.0000416
ExAC
AF:
0.00000825
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 28, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.383C>T (p.A128V) 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 383, causing the alanine (A) at amino acid position 128 to be replaced by a valine (V). 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
Benign
-0.27
T
BayesDel_noAF
Benign
-0.39
CADD
Benign
14
DANN
Benign
0.89
Eigen
Benign
-0.82
Eigen_PC
Benign
-0.79
FATHMM_MKL
Benign
0.054
N
LIST_S2
Benign
0.71
T;T;T
M_CAP
Benign
0.075
D
MetaRNN
Benign
0.068
T;T;T
MetaSVM
Benign
-0.42
T
MutationAssessor
Benign
0.41
N;N;N
PrimateAI
Benign
0.42
T
PROVEAN
Benign
-0.72
N;N;N
REVEL
Benign
0.19
Sift
Benign
0.14
T;T;T
Sift4G
Benign
0.29
T;T;T
Polyphen
0.0030
B;B;B
Vest4
0.12
MVP
0.69
MPC
0.19
ClinPred
0.028
T
GERP RS
0.88
gMVP
0.36

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs753690252; hg19: chr10-135193704; COSMIC: COSV53373969; API