20-4121153-C-T

Variant names:

• chr20-4121153-C-T
• rs1741344
• ENST00000493223.1:n.174C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 44 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 -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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMOX	ENST00000493223.1	n.174C>T		non_coding_transcript_exon_variant	Exon 1 of 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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 2 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.800 AC: 8 AN: 10

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.786 AC: 11 AN: 14

Other (OTH) AF: 0.750 AC: 3 AN: 4

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

African (AFR) AF: 0.571 AC: 23676 AN: 41458

American (AMR) AF: 0.718 AC: 10964 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.620 AC: 2153 AN: 3470

East Asian (EAS) AF: 0.798 AC: 4135 AN: 5182

South Asian (SAS) AF: 0.782 AC: 3769 AN: 4822

European-Finnish (FIN) AF: 0.660 AC: 6959 AN: 10544

Middle Eastern (MID) AF: 0.697 AC: 205 AN: 294

European-Non Finnish (NFE) AF: 0.645 AC: 43820 AN: 67958

Other (OTH) AF: 0.648 AC: 1367 AN: 2110

Alfa AF: 0.646 Hom.: 133569

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
PhyloP100		-0.15

Splicing

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

Other links and lift over

dbSNP: rs1741344; hg19: chr20-4101800;