Variant rs12066445 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_016178.2(OAZ3):c.305-115G>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
NM_016178.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.369

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:

ENSG00000249602 (HGNC:):

ENSG00000249602 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=-0.81).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.377 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	Protein	UniProt
TDRKH	XM_017000123.3 linkuse as main transcript	c.*2658C>T	3_prime_UTR_variant	14/14	XP_016855612.1	Q9Y2W6-2
TDRKH	XM_047441989.1 linkuse as main transcript	c.*2658C>T	3_prime_UTR_variant	14/14	XP_047297945.1
TDRKH	XM_047442008.1 linkuse as main transcript	c.*2658C>T	3_prime_UTR_variant	14/14	XP_047297964.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	Protein	UniProt
OAZ3	ENST00000400999.7 linkuse as main transcript	c.304-114G>A	intron_variant	5	ENSP00000383784.3	Q9UMX2-1A8MW57
OAZ3	ENST00000453029.2 linkuse as main transcript	c.208-114G>A	intron_variant	5	ENSP00000415904.2	H0Y7Y4
OAZ3	ENST00000321531.10 linkuse as main transcript	c.169-114G>A	intron_variant	5	ENSP00000313922.5	A0A0G2JH29
OAZ3	ENST00000479764.7 linkuse as main transcript	c.303+645G>A	intron_variant	5	ENSP00000463055.3	Q5SZR7
OAZ3	ENST00000635374.1 linkuse as main transcript	c.106-114G>A	intron_variant	5	ENSP00000489420.1	A0A0U1RRA2
OAZ3	ENST00000635322.1 linkuse as main transcript	c.168+645G>A	intron_variant	5	ENSP00000489350.1	A0A0U1RR57

Frequencies

GnomAD3 genomes

AF:

0.303

AC:

46047

AN:

151896

Hom.:

7488

Cov.:

show subpopulations

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.:

AF XY:

0.322

AC XY:

186760

AN XY:

579930

show subpopulations

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.:

AF XY:

0.306

AC XY:

22761

AN XY:

74276

show subpopulations

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

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