rs1781423

Positions:

• chr1-151770667-C-T

Variant summary

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

The ENST00000400999.7(OAZ3):​c.565+410C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 230,244 control chromosomes in the GnomAD database, including 22,316 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 0.41 (13833 hom., cov: 32)
  • Exomes 𝑓: 0.45 (8483 hom.)
• Consequence: OAZ3 ENST00000400999.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.352

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:11713): (tudor and KH domain containing) Predicted to enable RNA binding activity. Predicted to be involved in fertilization; gamete generation; and piRNA metabolic process. Predicted to be located in mitochondrion; pi-body; and piP-body. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.508 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OAZ3	NM_001134939.1	c.431+410C>T		intron_variant			NP_001128411.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OAZ3	ENST00000400999.7	c.565+410C>T		intron_variant		5		ENSP00000383784	P1

Frequencies

GnomAD3 genomes AF: 0.410 AC: 62334 AN: 151910 Hom.: 13834 Cov.: 32

Gnomad AFR AF: 0.276

Gnomad AMI AF: 0.574

Gnomad AMR AF: 0.334

Gnomad ASJ AF: 0.395

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.410

Gnomad FIN AF: 0.470

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.513

Gnomad OTH AF: 0.406

GnomAD4 exome AF: 0.449 AC: 35123 AN: 78216 Hom.: 8483 AF XY: 0.445 AC XY: 17765 AN XY: 39954

Gnomad4 AFR exome AF: 0.259

Gnomad4 AMR exome AF: 0.321

Gnomad4 ASJ exome AF: 0.404

Gnomad4 EAS exome AF: 0.229

Gnomad4 SAS exome AF: 0.384

Gnomad4 FIN exome AF: 0.467

Gnomad4 NFE exome AF: 0.496

Gnomad4 OTH exome AF: 0.418

GnomAD4 genome AF: 0.410 AC: 62334 AN: 152028 Hom.: 13833 Cov.: 32 AF XY: 0.404 AC XY: 30028 AN XY: 74310

Gnomad4 AFR AF: 0.276

Gnomad4 AMR AF: 0.334

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: 0.407

Alfa AF: 0.450 Hom.: 5445

Bravo AF: 0.393

Asia WGS AF: 0.345 AC: 1200 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.93
DANN	Benign	0.68

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: rs1781423; hg19: chr1-151743143;