Genetic Variant SMOX:p.Arg129Leu (chr20-4177528-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_175839.3(SMOX):c.386G>T(p.Arg129Leu) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R129H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SMOX
NM_175839.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.55

Publications

3 publications found

Variant links:

Genes affected

SMOX (HGNC:15862): (spermine oxidase) Polyamines are ubiquitous polycationic alkylamines which include spermine, spermidine, putrescine, and agmatine. These molecules participate in a broad range of cellular functions which include cell cycle modulation, scavenging reactive oxygen species, and the control of gene expression. These molecules also play important roles in neurotransmission through their regulation of cell-surface receptor activity, involvement in intracellular signalling pathways, and their putative roles as neurotransmitters. This gene encodes an FAD-containing enzyme that catalyzes the oxidation of spermine to spermadine and secondarily produces hydrogen peroxide. Multiple transcript variants encoding different isoenzymes have been identified for this gene, some of which have failed to demonstrate significant oxidase activity on natural polyamine substrates. The characterized isoenzymes have distinctive biochemical characteristics and substrate specificities, suggesting the existence of additional levels of complexity in polyamine catabolism. [provided by RefSeq, Jul 2012]

SMOX links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2485955).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_175839.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SMOX	NM_175839.3	MANE Select	c.386G>T	p.Arg129Leu	missense	Exon 3 of 7	NP_787033.1	Q9NWM0-1
SMOX	NM_001270691.2		c.386G>T	p.Arg129Leu	missense	Exon 3 of 8	NP_001257620.1	Q9NWM0-6
SMOX	NM_175842.3		c.386G>T	p.Arg129Leu	missense	Exon 3 of 9	NP_787036.1	Q9NWM0-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SMOX	ENST00000305958.9	TSL:1 MANE Select	c.386G>T	p.Arg129Leu	missense	Exon 3 of 7	ENSP00000307252.4	Q9NWM0-1
SMOX	ENST00000621355.4	TSL:1	c.386G>T	p.Arg129Leu	missense	Exon 3 of 8	ENSP00000478305.1	Q9NWM0-6
SMOX	ENST00000278795.7	TSL:1	c.386G>T	p.Arg129Leu	missense	Exon 3 of 9	ENSP00000278795.3	Q9NWM0-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1444626

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

716692

African (AFR)

AF:

0.00

AC:

AN:

33328

American (AMR)

AF:

0.00

AC:

AN:

42314

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25794

East Asian (EAS)

AF:

0.00

AC:

AN:

39264

South Asian (SAS)

AF:

0.00

AC:

AN:

83342

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52200

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1102902

Other (OTH)

AF:

0.00

AC:

AN:

59728

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Uncertain

0.025

BayesDel_noAF

Benign

-0.20

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Pathogenic

0.81

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.62

FATHMM_MKL

Uncertain

0.77

LIST_S2

Uncertain

0.96

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.25

MetaSVM

Benign

-0.47

MutationAssessor

Uncertain

2.1

PhyloP100

1.6

PrimateAI

Benign

0.21

PROVEAN

Uncertain

-3.7

REVEL

Benign

0.23

Sift

Benign

0.15

Sift4G

Benign

0.24

Polyphen

0.022

Vest4

0.36

MutPred

0.60

Loss of methylation at K133 (P = 0.0497)

MVP

0.28

MPC

0.78

ClinPred

0.30

GERP RS

-2.3

PromoterAI

-0.0096

Neutral

(source)

Varity_R

0.12

gMVP

0.73

Mutation Taster

=91/9

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over