rs4995159

chr1-151770018-A-G

Variant summary

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

The ENST00000400999.7(OAZ3):c.480-154A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.499 in 1,282,842 control chromosomes in the GnomAD database, including 163,823 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 0.42 (14073 hom., cov: 33)
  • Exomes 𝑓: 0.51 (149750 hom.)
• Consequence: OAZ3 ENST00000400999.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.89

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]

TDRKH (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.509 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OAZ3	NM_001134939.1	c.346-154A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OAZ3	ENST00000400999.7	c.480-154A>G		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.415 AC: 63136 AN: 151962 Hom.: 14072 Cov.: 33

Gnomad AFR AF: 0.294

Gnomad AMI AF: 0.574

Gnomad AMR AF: 0.336

Gnomad ASJ AF: 0.395

Gnomad EAS AF: 0.222

Gnomad SAS AF: 0.410

Gnomad FIN AF: 0.470

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.513

Gnomad OTH AF: 0.409

GnomAD4 exome AF: 0.511 AC: 577581 AN: 1130762 Hom.: 149750 AF XY: 0.508 AC XY: 290784 AN XY: 572830

Gnomad4 AFR exome AF: 0.308

Gnomad4 AMR exome AF: 0.296

Gnomad4 ASJ exome AF: 0.431

Gnomad4 EAS exome AF: 0.253

Gnomad4 SAS exome AF: 0.421

Gnomad4 FIN exome AF: 0.507

Gnomad4 NFE exome AF: 0.549

Gnomad4 OTH exome AF: 0.474

GnomAD4 genome AF: 0.415 AC: 63137 AN: 152080 Hom.: 14073 Cov.: 33 AF XY: 0.410 AC XY: 30445 AN XY: 74338

Gnomad4 AFR AF: 0.293

Gnomad4 AMR AF: 0.335

Gnomad4 ASJ AF: 0.395

Gnomad4 EAS AF: 0.221

Gnomad4 SAS AF: 0.410

Gnomad4 FIN AF: 0.470

Gnomad4 NFE AF: 0.513

Gnomad4 OTH AF: 0.410

Alfa AF: 0.472 Hom.: 2137

Bravo AF: 0.399

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	1.3
Dann	Benign	0.17

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: rs4995159; hg19: chr1-151742494;