20-4121153-C-T

Position:

• chr20-4121153-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000493223.1(SMOX):​n.174C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.642 in 152,054 control chromosomes in the GnomAD database, including 31,510 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 0.64 (31501 hom., cov: 32)
  • Exomes 𝑓: 0.80 (9 hom.)
• Consequence: SMOX ENST00000493223.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.149

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.778 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMOX	ENST00000493223.1	n.174C>T		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes AF: 0.642 AC: 97556 AN: 151906 Hom.: 31462 Cov.: 32

Gnomad AFR AF: 0.571

Gnomad AMI AF: 0.649

Gnomad AMR AF: 0.718

Gnomad ASJ AF: 0.620

Gnomad EAS AF: 0.798

Gnomad SAS AF: 0.781

Gnomad FIN AF: 0.660

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.645

Gnomad OTH AF: 0.647

GnomAD4 exome AF: 0.800 AC: 24 AN: 30 Hom.: 9 Cov.: 0 AF XY: 0.792 AC XY: 19 AN XY: 24

Gnomad4 ASJ exome AF: 1.00

Gnomad4 FIN exome AF: 0.800

Gnomad4 NFE exome AF: 0.786

Gnomad4 OTH exome AF: 0.750

GnomAD4 genome AF: 0.642 AC: 97640 AN: 152024 Hom.: 31501 Cov.: 32 AF XY: 0.650 AC XY: 48325 AN XY: 74290

Gnomad4 AFR AF: 0.571

Gnomad4 AMR AF: 0.718

Gnomad4 ASJ AF: 0.620

Gnomad4 EAS AF: 0.798

Gnomad4 SAS AF: 0.782

Gnomad4 FIN AF: 0.660

Gnomad4 NFE AF: 0.645

Gnomad4 OTH AF: 0.648

Alfa AF: 0.651 Hom.: 71048

Bravo AF: 0.642

Asia WGS AF: 0.808 AC: 2805 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	13
DANN	Benign	0.88

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1741344; hg19: chr20-4101800;