rs6052399

chr20-4146356-T-Cchr20-4146356-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000493223.1(SMOX):n.205+25172T>C variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0879 in 152,198 control chromosomes in the GnomAD database, including 791 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 0.088 (791 hom., cov: 32)
• Consequence: SMOX ENST00000493223.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.216

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMOX	ENST00000493223.1	n.205+25172T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0879 AC: 13369 AN: 152080 Hom.: 793 Cov.: 32

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.0717

Gnomad EAS AF: 0.0887

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.0523

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0423

Gnomad OTH AF: 0.0922

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0879 AC: 13384 AN: 152198 Hom.: 791 Cov.: 32 AF XY: 0.0890 AC XY: 6624 AN XY: 74410

Gnomad4 AFR AF: 0.159

Gnomad4 AMR AF: 0.117

Gnomad4 ASJ AF: 0.0717

Gnomad4 EAS AF: 0.0889

Gnomad4 SAS AF: 0.132

Gnomad4 FIN AF: 0.0523

Gnomad4 NFE AF: 0.0423

Gnomad4 OTH AF: 0.0907

Alfa AF: 0.0498 Hom.: 254

Bravo AF: 0.0960

Asia WGS AF: 0.104 AC: 360 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	7.9
Dann	Benign	0.79

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs6052399; hg19: chr20-4127003;