20-4177368-C-T

Variant names:

• chr20-4177368-C-T
• rs972488683
• NM_175839.3:c.226C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_175839.3(SMOX):​c.226C>T​(p.Leu76Leu) variant causes a synonymous change. The variant allele was found at a frequency of 0.000000714 in 1,400,306 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: SMOX NM_175839.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.12
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_175839.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMOX	NM_175839.3	MANE Select	c.226C>T	p.Leu76Leu	synonymous	Exon 3 of 7	NP_787033.1	Q9NWM0-1
	SMOX	NM_001270691.2		c.226C>T	p.Leu76Leu	synonymous	Exon 3 of 8	NP_001257620.1	Q9NWM0-6
	SMOX	NM_175842.3		c.226C>T	p.Leu76Leu	synonymous	Exon 3 of 9	NP_787036.1	Q9NWM0-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMOX	ENST00000305958.9	TSL:1 MANE Select	c.226C>T	p.Leu76Leu	synonymous	Exon 3 of 7	ENSP00000307252.4	Q9NWM0-1
	SMOX	ENST00000621355.4	TSL:1	c.226C>T	p.Leu76Leu	synonymous	Exon 3 of 8	ENSP00000478305.1	Q9NWM0-6
	SMOX	ENST00000278795.7	TSL:1	c.226C>T	p.Leu76Leu	synonymous	Exon 3 of 9	ENSP00000278795.3	Q9NWM0-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.14e-7 AC: 1 AN: 1400306 Hom.: 0 Cov.: 31 AF XY: 0.00000145 AC XY: 1 AN XY: 690726

African (AFR) AF: 0.00 AC: 0 AN: 31676

American (AMR) AF: 0.00 AC: 0 AN: 35792

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25180

East Asian (EAS) AF: 0.00 AC: 0 AN: 35860

South Asian (SAS) AF: 0.00 AC: 0 AN: 79270

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49352

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5700

European-Non Finnish (NFE) AF: 9.26e-7 AC: 1 AN: 1079430

Other (OTH) AF: 0.00 AC: 0 AN: 58046

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	12
DANN	Benign	0.76
PhyloP100		6.1
PromoterAI		-0.0081	Neutral

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: rs972488683; hg19: chr20-4158015;