Variant 1-151770322-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000400999.7(OAZ3):c.565+65T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 1,553,996 control chromosomes in the GnomAD database, including 83,541 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 0.32 ( 8010 hom., cov: 31)

Exomes 𝑓: 0.33 ( 75531 hom. )

Consequence

OAZ3
ENST00000400999.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.101

Variant links:

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]

OAZ3 links:

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]

TDRKH links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.383 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OAZ3	NM_001134939.1 linkuse as main transcript	c.431+65T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OAZ3	ENST00000400999.7 linkuse as main transcript	c.565+65T>C		intron_variant		5		P1	Q9UMX2-1

Frequencies

GnomAD3 genomes

AF:

0.317

AC:

48083

AN:

151864

Hom.:

7996

Cov.:

show subpopulations

Gnomad AFR

AF:

0.248

Gnomad AMI

AF:

0.209

Gnomad AMR

AF:

0.391

Gnomad ASJ

AF:

0.502

Gnomad EAS

AF:

0.270

Gnomad SAS

AF:

0.255

Gnomad FIN

AF:

0.361

Gnomad MID

AF:

0.440

Gnomad NFE

AF:

0.333

Gnomad OTH

AF:

0.352

GnomAD4 exome

AF:

0.326

AC:

456513

AN:

1402014

Hom.:

75531

Cov.:

AF XY:

0.326

AC XY:

225924

AN XY:

693018

show subpopulations

Gnomad4 AFR exome

AF:

0.245

Gnomad4 AMR exome

AF:

0.365

Gnomad4 ASJ exome

AF:

0.485

Gnomad4 EAS exome

AF:

0.285

Gnomad4 SAS exome

AF:

0.278

Gnomad4 FIN exome

AF:

0.358

Gnomad4 NFE exome

AF:

0.325

Gnomad4 OTH exome

AF:

0.338

GnomAD4 genome

AF:

0.317

AC:

48141

AN:

151982

Hom.:

8010

Cov.:

AF XY:

0.319

AC XY:

23728

AN XY:

74280

show subpopulations

Gnomad4 AFR

AF:

0.248

Gnomad4 AMR

AF:

0.392

Gnomad4 ASJ

AF:

0.502

Gnomad4 EAS

AF:

0.270

Gnomad4 SAS

AF:

0.256

Gnomad4 FIN

AF:

0.361

Gnomad4 NFE

AF:

0.333

Gnomad4 OTH

AF:

0.354

Alfa

AF:

0.330

Hom.:

1994

Bravo

AF:

0.312

Asia WGS

AF:

0.262

AC:

912

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Benign

0.77

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over