20-4182727-G-T

Variant names:

• chr20-4182727-G-T
• rs147924124
• NM_175839.3:c.1248G>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_175839.3(SMOX):​c.1248G>T​(p.Pro416Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0017 in 1,614,150 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0013 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (6 hom.)
• Consequence: SMOX NM_175839.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.95

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 20-4182727-G-T is Benign according to our data. Variant chr20-4182727-G-T is described in ClinVar as [Benign]. Clinvar id is 714118.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.95 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMOX	NM_175839.3	c.1248G>T	p.Pro416Pro	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.1248G>T	p.Pro416Pro	synonymous_variant	Exon 5 of 7	1	NM_175839.3	ENSP00000307252.4

Frequencies

GnomAD3 genomes AF: 0.00133 AC: 203 AN: 152150 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000603

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00123

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00229

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.00124 AC: 312 AN: 251448 AF XY: 0.00111

Gnomad AFR exome AF: 0.000492

Gnomad AMR exome AF: 0.000231

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00217

Gnomad NFE exome AF: 0.00205

Gnomad OTH exome AF: 0.00196

GnomAD4 exome AF: 0.00174 AC: 2539 AN: 1461882 Hom.: 6 Cov.: 35 AF XY: 0.00169 AC XY: 1229 AN XY: 727242

Gnomad4 AFR exome AF: 0.000209 AC: 7 AN: 33480

Gnomad4 AMR exome AF: 0.000246 AC: 11 AN: 44724

Gnomad4 ASJ exome AF: 0.000230 AC: 6 AN: 26136

Gnomad4 EAS exome AF: 0.0000252 AC: 1 AN: 39700

Gnomad4 SAS exome AF: 0.000128 AC: 11 AN: 86258

Gnomad4 FIN exome AF: 0.00219 AC: 117 AN: 53410

Gnomad4 NFE exome AF: 0.00207 AC: 2300 AN: 1112010

Gnomad4 Remaining exome AF: 0.00139 AC: 84 AN: 60396

GnomAD4 genome AF: 0.00133 AC: 203 AN: 152268 Hom.: 1 Cov.: 32 AF XY: 0.00110 AC XY: 82 AN XY: 74456

Gnomad4 AFR AF: 0.000602 AC: 0.000601569 AN: 0.000601569

Gnomad4 AMR AF: 0.000327 AC: 0.000326797 AN: 0.000326797

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.000415 AC: 0.000414938 AN: 0.000414938

Gnomad4 FIN AF: 0.00123 AC: 0.00122572 AN: 0.00122572

Gnomad4 NFE AF: 0.00229 AC: 0.00229338 AN: 0.00229338

Gnomad4 OTH AF: 0.000946 AC: 0.000946074 AN: 0.000946074

Alfa AF: 0.00140 Hom.: 0

Bravo AF: 0.00114

EpiCase AF: 0.00158

EpiControl AF: 0.00172

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	1.0
DANN	Benign	0.69
Mutation Taster		=96/4	polymorphism

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: rs147924124; hg19: chr20-4163374;