20-4179128-T-G

Position:

• chr20-4179128-T-G

Variant summary

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

The ENST00000305958.9(SMOX):​c.435+1551T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.54 in 152,018 control chromosomes in the GnomAD database, including 22,802 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 0.54 (22802 hom., cov: 32)
• Consequence: SMOX ENST00000305958.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.65 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMOX	NM_175839.3	c.435+1551T>G		intron_variant		ENST00000305958.9	NP_787033.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMOX	ENST00000305958.9	c.435+1551T>G		intron_variant		1	NM_175839.3	ENSP00000307252	P4

Frequencies

GnomAD3 genomes AF: 0.540 AC: 82070 AN: 151900 Hom.: 22767 Cov.: 32

Gnomad AFR AF: 0.656

Gnomad AMI AF: 0.584

Gnomad AMR AF: 0.566

Gnomad ASJ AF: 0.420

Gnomad EAS AF: 0.549

Gnomad SAS AF: 0.324

Gnomad FIN AF: 0.517

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.490

Gnomad OTH AF: 0.486

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

GnomAD4 genome AF: 0.540 AC: 82154 AN: 152018 Hom.: 22802 Cov.: 32 AF XY: 0.538 AC XY: 39988 AN XY: 74324

Gnomad4 AFR AF: 0.656

Gnomad4 AMR AF: 0.566

Gnomad4 ASJ AF: 0.420

Gnomad4 EAS AF: 0.550

Gnomad4 SAS AF: 0.324

Gnomad4 FIN AF: 0.517

Gnomad4 NFE AF: 0.490

Gnomad4 OTH AF: 0.481

Alfa AF: 0.504 Hom.: 15285

Bravo AF: 0.553

Asia WGS AF: 0.441 AC: 1532 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	3.5
DANN	Benign	0.79

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: rs1765017; hg19: chr20-4159775;