20-4177709-A-G

Variant names:

• chr20-4177709-A-G
• rs1622950
• NM_175839.3:c.435+132A>G

Variant summary

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

The NM_175839.3(SMOX):​c.435+132A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.523 in 781,450 control chromosomes in the GnomAD database, including 108,608 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 0.55 (23553 hom., cov: 32)
  • Exomes 𝑓: 0.52 (85055 hom.)
• Consequence: SMOX NM_175839.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0400

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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.645 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMOX	NM_175839.3	c.435+132A>G		intron_variant	Intron 3 of 6	ENST00000305958.9	NP_787033.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMOX	ENST00000305958.9	c.435+132A>G		intron_variant	Intron 3 of 6	1	NM_175839.3	ENSP00000307252.4

Frequencies

GnomAD3 genomes AF: 0.551 AC: 83699 AN: 151898 Hom.: 23529 Cov.: 32

Gnomad AFR AF: 0.631

Gnomad AMI AF: 0.634

Gnomad AMR AF: 0.599

Gnomad ASJ AF: 0.490

Gnomad EAS AF: 0.663

Gnomad SAS AF: 0.347

Gnomad FIN AF: 0.522

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.506

Gnomad OTH AF: 0.502

GnomAD4 exome AF: 0.516 AC: 324552 AN: 629434 Hom.: 85055 AF XY: 0.508 AC XY: 164103 AN XY: 322950

Gnomad4 AFR exome AF: 0.634

Gnomad4 AMR exome AF: 0.636

Gnomad4 ASJ exome AF: 0.504

Gnomad4 EAS exome AF: 0.688

Gnomad4 SAS exome AF: 0.351

Gnomad4 FIN exome AF: 0.536

Gnomad4 NFE exome AF: 0.510

Gnomad4 OTH exome AF: 0.525

GnomAD4 genome AF: 0.551 AC: 83763 AN: 152016 Hom.: 23553 Cov.: 32 AF XY: 0.549 AC XY: 40760 AN XY: 74298

Gnomad4 AFR AF: 0.631

Gnomad4 AMR AF: 0.599

Gnomad4 ASJ AF: 0.490

Gnomad4 EAS AF: 0.664

Gnomad4 SAS AF: 0.347

Gnomad4 FIN AF: 0.522

Gnomad4 NFE AF: 0.506

Gnomad4 OTH AF: 0.498

Alfa AF: 0.522 Hom.: 4141

Bravo AF: 0.566

Asia WGS AF: 0.492 AC: 1709 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	3.5
DANN	Benign	0.71

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: rs1622950; hg19: chr20-4158356;