rs370515510

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_175839.3(SMOX):c.386G>A(p.Arg129His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000319 in 1,596,798 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

SMOX
NM_175839.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

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: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.104299664).

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>A	p.Arg129His	missense	Exon 3 of 7	NP_787033.1	Q9NWM0-1
SMOX	NM_001270691.2		c.386G>A	p.Arg129His	missense	Exon 3 of 8	NP_001257620.1	Q9NWM0-6
SMOX	NM_175842.3		c.386G>A	p.Arg129His	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>A	p.Arg129His	missense	Exon 3 of 7	ENSP00000307252.4	Q9NWM0-1
SMOX	ENST00000621355.4	TSL:1	c.386G>A	p.Arg129His	missense	Exon 3 of 8	ENSP00000478305.1	Q9NWM0-6
SMOX	ENST00000278795.7	TSL:1	c.386G>A	p.Arg129His	missense	Exon 3 of 9	ENSP00000278795.3	Q9NWM0-4

Frequencies

GnomAD3 genomes

AF:

0.0000920

AC:

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000493

AC:

AN:

223268

AF XY:

0.0000500

show subpopulations

Gnomad AFR exome

AF:

0.000212

Gnomad AMR exome

AF:

0.0000631

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000117

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000256

AC:

AN:

1444626

Hom.:

Cov.:

AF XY:

0.0000251

AC XY:

AN XY:

716692

show subpopulations

African (AFR)

AF:

0.000270

AC:

AN:

33328

American (AMR)

AF:

0.0000473

AC:

AN:

42314

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25794

East Asian (EAS)

AF:

0.0000509

AC:

AN:

39264

South Asian (SAS)

AF:

0.000108

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:

0.0000118

AC:

AN:

1102902

Other (OTH)

AF:

0.0000335

AC:

AN:

59728

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000920

AC:

AN:

152172

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.000241

AC:

AN:

41438

American (AMR)

AF:

0.00

AC:

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000192

AC:

AN:

5204

South Asian (SAS)

AF:

0.000207

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68022

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.561

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000581

Hom.:

Bravo

AF:

0.000102

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000577

AC:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.25

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.72

Eigen

Benign

-0.81

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.52

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.039

MetaRNN

Benign

0.10

MetaSVM

Benign

-0.57

MutationAssessor

Benign

1.7

PhyloP100

1.6

PrimateAI

Benign

0.21

PROVEAN

Benign

-2.2

REVEL

Benign

0.24

Sift

Benign

0.12

Sift4G

Benign

0.14

Polyphen

0.0

Vest4

0.21

MVP

0.23

MPC

0.64

ClinPred

0.032

GERP RS

-2.3

PromoterAI

-0.020

Neutral

(source)

Varity_R

0.037

gMVP

0.56

Mutation Taster

=94/6

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over