20-4182190-G-T

Variant names:

• chr20-4182190-G-T
• rs114897412
• NM_175839.3:c.711G>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_175839.3(SMOX):​c.711G>T​(p.Ser237Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00423 in 1,613,516 control chromosomes in the GnomAD database, including 245 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.023 (120 hom., cov: 32)
  • Exomes 𝑓: 0.0023 (125 hom.)
• Consequence: SMOX NM_175839.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -6.22

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 20-4182190-G-T is Benign according to our data. Variant chr20-4182190-G-T is described in ClinVar as [Benign]. Clinvar id is 782665.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-6.22 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0756 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMOX	NM_175839.3	c.711G>T	p.Ser237Ser	synonymous_variant	Exon 5 of 7	ENST00000305958.9	NP_787033.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMOX	ENST00000305958.9	c.711G>T	p.Ser237Ser	synonymous_variant	Exon 5 of 7	1	NM_175839.3	ENSP00000307252.4

Frequencies

GnomAD3 genomes AF: 0.0226 AC: 3441 AN: 152090 Hom.: 120 Cov.: 32

Gnomad AFR AF: 0.0781

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0105

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.0172

GnomAD2 exomes AF: 0.00566 AC: 1416 AN: 250298 AF XY: 0.00385

Gnomad AFR exome AF: 0.0793

Gnomad AMR exome AF: 0.00304

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000124

Gnomad OTH exome AF: 0.00212

GnomAD4 exome AF: 0.00232 AC: 3389 AN: 1461308 Hom.: 125 Cov.: 37 AF XY: 0.00191 AC XY: 1389 AN XY: 726994

Gnomad4 AFR exome AF: 0.0835 AC: 2796 AN: 33480

Gnomad4 AMR exome AF: 0.00414 AC: 185 AN: 44714

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 26134

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 39698

Gnomad4 SAS exome AF: 0.000104 AC: 9 AN: 86258

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 52876

Gnomad4 NFE exome AF: 0.0000513 AC: 57 AN: 1111986

Gnomad4 Remaining exome AF: 0.00550 AC: 332 AN: 60394

GnomAD4 genome AF: 0.0226 AC: 3439 AN: 152208 Hom.: 120 Cov.: 32 AF XY: 0.0218 AC XY: 1621 AN XY: 74430

Gnomad4 AFR AF: 0.0778 AC: 0.0778404 AN: 0.0778404

Gnomad4 AMR AF: 0.0105 AC: 0.0104548 AN: 0.0104548

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.000207 AC: 0.000206954 AN: 0.000206954

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.000147 AC: 0.000147011 AN: 0.000147011

Gnomad4 OTH AF: 0.0170 AC: 0.0170293 AN: 0.0170293

Alfa AF: 0.00921 Hom.: 69

Bravo AF: 0.0261

Asia WGS AF: 0.00346 AC: 12 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 29, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.011
DANN	Benign	0.67
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
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

Publications

LitVar

Other links and lift over

dbSNP: rs114897412; hg19: chr20-4162837;