rs12066445

chr1-151767944-G-Achr1-151767944-G-C

Variant summary

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

The ENST00000400999.7(OAZ3):c.304-114G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 1,323,092 control chromosomes in the GnomAD database, including 69,368 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 0.30 (7498 hom., cov: 32)
  • Exomes 𝑓: 0.32 (61870 hom.)
• Consequence: OAZ3 ENST00000400999.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.369

Genes affected

OAZ3 (HGNC:8097): (ornithine decarboxylase antizyme 3) The protein encoded by this gene belongs to the ornithine decarboxylase antizyme family, which plays a role in cell growth and proliferation by regulating intracellular polyamine levels. Expression of antizymes requires +1 ribosomal frameshifting, which is enhanced by high levels of polyamines. Antizymes in turn bind to and inhibit ornithine decarboxylase (ODC), the key enzyme in polyamine biosynthesis; thus, completing the auto-regulatory circuit. This gene encodes antizyme 3, the third member of the antizyme family. Like antizymes 1 and 2, antizyme 3 inhibits ODC activity and polyamine uptake; however, it does not stimulate ODC degradation. Also, while antizymes 1 and 2 have broad tissue distribution, expression of antizyme 3 is restricted to haploid germ cells in testis, suggesting a distinct role for this antizyme in spermiogenesis. Antizyme 3 gene knockout studies showed that homozygous mutant male mice were infertile, and indicated the likely role of this antizyme in the formation of a rigid connection between the sperm head and tail during spermatogenesis. Alternatively spliced transcript variants encoding different isoforms, including one resulting from the use of non-AUG (CUG) translation initiation codon, have been found for this gene. [provided by RefSeq, Dec 2014]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.377 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OAZ3	NM_001134939.1	c.170-114G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OAZ3	ENST00000400999.7	c.304-114G>A		intron_variant		5		P1
	ENST00000512280.1	n.264+194C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.303 AC: 46047 AN: 151896 Hom.: 7488 Cov.: 32

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.210

Gnomad AMR AF: 0.384

Gnomad ASJ AF: 0.482

Gnomad EAS AF: 0.256

Gnomad SAS AF: 0.255

Gnomad FIN AF: 0.362

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.332

Gnomad OTH AF: 0.339

GnomAD4 exome AF: 0.322 AC: 376546 AN: 1171080 Hom.: 61870 Cov.: 16 AF XY: 0.322 AC XY: 186760 AN XY: 579930

Gnomad4 AFR exome AF: 0.199

Gnomad4 AMR exome AF: 0.363

Gnomad4 ASJ exome AF: 0.462

Gnomad4 EAS exome AF: 0.276

Gnomad4 SAS exome AF: 0.277

Gnomad4 FIN exome AF: 0.358

Gnomad4 NFE exome AF: 0.323

Gnomad4 OTH exome AF: 0.329

GnomAD4 genome AF: 0.303 AC: 46087 AN: 152012 Hom.: 7498 Cov.: 32 AF XY: 0.306 AC XY: 22761 AN XY: 74276

Gnomad4 AFR AF: 0.206

Gnomad4 AMR AF: 0.385

Gnomad4 ASJ AF: 0.482

Gnomad4 EAS AF: 0.257

Gnomad4 SAS AF: 0.256

Gnomad4 FIN AF: 0.362

Gnomad4 NFE AF: 0.332

Gnomad4 OTH AF: 0.341

Alfa AF: 0.324 Hom.: 4675

Bravo AF: 0.296

Asia WGS AF: 0.246 AC: 859 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	6.8
Dann	Benign	0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs12066445; hg19: chr1-151740420; COSMIC: COSV58617295; COSMIC: COSV58617295;