Genetic Variant OAZ3:c.480-94A>G (chr1-151770078-A-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_016178.2(OAZ3):c.480-94A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.00059 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0011 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

OAZ3
NM_016178.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.78

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 Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.04).

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein	UniProt
TDRKH	XM_017000123.3 link	c.*524T>C	3_prime_UTR_variant	Exon 14 of 14	XP_016855612.1	Q9Y2W6-2
TDRKH	XM_047441989.1 link	c.*524T>C	3_prime_UTR_variant	Exon 14 of 14	XP_047297945.1
TDRKH	XM_047442008.1 link	c.*524T>C	3_prime_UTR_variant	Exon 14 of 14	XP_047297964.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
OAZ3	ENST00000400999.7 link	c.480-94A>G	intron_variant	Intron 4 of 5	5	ENSP00000383784.3	Q9UMX2-1A8MW57
OAZ3	ENST00000453029.2 link	c.384-94A>G	intron_variant	Intron 4 of 5	5	ENSP00000415904.2	H0Y7Y4
OAZ3	ENST00000321531.10 link	c.345-94A>G	intron_variant	Intron 4 of 5	5	ENSP00000313922.5	A0A0G2JH29
OAZ3	ENST00000479764.7 link	c.304-94A>G	intron_variant	Intron 3 of 4	5	ENSP00000463055.3	Q5SZR7
OAZ3	ENST00000635374.1 link	c.282-999A>G	intron_variant	Intron 3 of 3	5	ENSP00000489420.1	A0A0U1RRA2
OAZ3	ENST00000635322.1 link	c.169-94A>G	intron_variant	Intron 3 of 4	5	ENSP00000489350.1	A0A0U1RR57

Frequencies

GnomAD3 genomes

AF:

0.000592

AC:

AN:

54088

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000441

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00285

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000853

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00111

AC:

439

AN:

395554

Hom.:

Cov.:

AF XY:

0.00107

AC XY:

211

AN XY:

197992

show subpopulations

Gnomad4 AFR exome

AF:

0.000296

Gnomad4 AMR exome

AF:

0.000432

Gnomad4 ASJ exome

AF:

0.000445

Gnomad4 EAS exome

AF:

0.00213

Gnomad4 SAS exome

AF:

0.000324

Gnomad4 FIN exome

AF:

0.000429

Gnomad4 NFE exome

AF:

0.00129

Gnomad4 OTH exome

AF:

0.00110

GnomAD4 genome

AF:

0.000590

AC:

AN:

54206

Hom.:

Cov.:

AF XY:

0.000703

AC XY:

AN XY:

27012

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.000439

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00285

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000853

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0529

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

4.0

DANN

Benign

0.073

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

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