chr20-4177709-A-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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 -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

African (AFR) AF: 0.634 AC: 10186 AN: 16074

American (AMR) AF: 0.636 AC: 13619 AN: 21422

Ashkenazi Jewish (ASJ) AF: 0.504 AC: 7753 AN: 15388

East Asian (EAS) AF: 0.688 AC: 21967 AN: 31912

South Asian (SAS) AF: 0.351 AC: 17394 AN: 49498

European-Finnish (FIN) AF: 0.536 AC: 16778 AN: 31280

Middle Eastern (MID) AF: 0.491 AC: 1194 AN: 2430

European-Non Finnish (NFE) AF: 0.510 AC: 218872 AN: 429440

Other (OTH) AF: 0.525 AC: 16789 AN: 31990

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

African (AFR) AF: 0.631 AC: 26135 AN: 41442

American (AMR) AF: 0.599 AC: 9146 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.490 AC: 1702 AN: 3470

East Asian (EAS) AF: 0.664 AC: 3428 AN: 5166

South Asian (SAS) AF: 0.347 AC: 1675 AN: 4822

European-Finnish (FIN) AF: 0.522 AC: 5514 AN: 10564

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.506 AC: 34380 AN: 67968

Other (OTH) AF: 0.498 AC: 1052 AN: 2114

Alfa AF: 0.530 Hom.: 7823

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
PhyloP100		0.040
PromoterAI		0.0083	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1622950; hg19: chr20-4158356;