rs1535225

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
SMOX	NM_175839.3	c.209-145G>A		intron_variant		ENST00000305958.9	NP_787033.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMOX	ENST00000305958.9	c.209-145G>A		intron_variant		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

Gnomad4 AFR exome AF: 0.580

Gnomad4 AMR exome AF: 0.305

Gnomad4 ASJ exome AF: 0.357

Gnomad4 EAS exome AF: 0.337

Gnomad4 SAS exome AF: 0.448

Gnomad4 FIN exome AF: 0.216

Gnomad4 NFE exome AF: 0.265

Gnomad4 OTH exome AF: 0.305

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

Gnomad4 AFR AF: 0.566

Gnomad4 AMR AF: 0.316

Gnomad4 ASJ AF: 0.366

Gnomad4 EAS AF: 0.318

Gnomad4 SAS AF: 0.442

Gnomad4 FIN AF: 0.220

Gnomad4 NFE AF: 0.272

Gnomad4 OTH AF: 0.348

Alfa AF: 0.226 Hom.: 954

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

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

Other links and lift over

dbSNP: rs1535225; hg19: chr20-4157853;