rs1535225

Variant names:

• chr20-4177206-G-A
• rs1535225
• NM_175839.3:c.209-145G>A

Your query was ambiguous. Multiple possible variants found:

• chr20-4177206-G-A
• chr20-4177206-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_175839.3(SMOX):​c.209-145G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 700,888 control chromosomes in the GnomAD database, including 36,974 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.36 (11331 hom., cov: 32)
  • Exomes 𝑓: 0.30 (25643 hom.)
• Consequence: SMOX NM_175839.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.301
• Publications: 3 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.56 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMOX	NM_175839.3	c.209-145G>A		intron_variant	Intron 2 of 6	ENST00000305958.9	NP_787033.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMOX	ENST00000305958.9	c.209-145G>A		intron_variant	Intron 2 of 6	1	NM_175839.3	ENSP00000307252.4

Frequencies

GnomAD3 genomes AF: 0.363 AC: 55133 AN: 151894 Hom.: 11309 Cov.: 32

Gnomad AFR AF: 0.566

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.316

Gnomad ASJ AF: 0.366

Gnomad EAS AF: 0.317

Gnomad SAS AF: 0.441

Gnomad FIN AF: 0.220

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.350

GnomAD4 exome AF: 0.295 AC: 162125 AN: 548876 Hom.: 25643 AF XY: 0.303 AC XY: 86091 AN XY: 284238

African (AFR) AF: 0.580 AC: 8160 AN: 14070

American (AMR) AF: 0.305 AC: 5768 AN: 18902

Ashkenazi Jewish (ASJ) AF: 0.357 AC: 5130 AN: 14366

East Asian (EAS) AF: 0.337 AC: 10621 AN: 31508

South Asian (SAS) AF: 0.448 AC: 20816 AN: 46516

European-Finnish (FIN) AF: 0.216 AC: 8148 AN: 37686

Middle Eastern (MID) AF: 0.347 AC: 916 AN: 2636

European-Non Finnish (NFE) AF: 0.265 AC: 93714 AN: 354124

Other (OTH) AF: 0.305 AC: 8852 AN: 29068

GnomAD4 genome AF: 0.363 AC: 55215 AN: 152012 Hom.: 11331 Cov.: 32 AF XY: 0.362 AC XY: 26922 AN XY: 74278

African (AFR) AF: 0.566 AC: 23433 AN: 41418

American (AMR) AF: 0.316 AC: 4831 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.366 AC: 1270 AN: 3470

East Asian (EAS) AF: 0.318 AC: 1637 AN: 5154

South Asian (SAS) AF: 0.442 AC: 2130 AN: 4816

European-Finnish (FIN) AF: 0.220 AC: 2332 AN: 10586

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.272 AC: 18458 AN: 67980

Other (OTH) AF: 0.348 AC: 732 AN: 2102

Alfa AF: 0.291 Hom.: 9692

Bravo AF: 0.375

Asia WGS AF: 0.360 AC: 1256 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.6
DANN	Benign	0.39
PhyloP100		0.30
PromoterAI		0.042	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1535225; hg19: chr20-4157853;