1-151770484-G-C

Position:

• chr1-151770484-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_016178.2(OAZ3):​c.565+227G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000187 in 503,504 control chromosomes in the GnomAD database, including 1 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 0.00013 (1 hom., cov: 31)
  • Exomes 𝑓: 0.00021 (0 hom.)
• Consequence: OAZ3 NM_016178.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.569

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TDRKH	XM_017000123.3	c.*118C>G		3_prime_UTR_variant	14/14		XP_016855612.1
TDRKH	XM_047441989.1	c.*118C>G		3_prime_UTR_variant	14/14		XP_047297945.1
TDRKH	XM_047442008.1	c.*118C>G		3_prime_UTR_variant	14/14		XP_047297964.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OAZ3	ENST00000400999.7	c.565+227G>C		intron_variant		5		ENSP00000383784.3
OAZ3	ENST00000453029.2	c.469+227G>C		intron_variant		5		ENSP00000415904.2
OAZ3	ENST00000321531.10	c.430+227G>C		intron_variant		5		ENSP00000313922.5
OAZ3	ENST00000479764.7	c.*14+227G>C		intron_variant		5		ENSP00000463055.3
OAZ3	ENST00000635374.1	c.282-593G>C		intron_variant		5		ENSP00000489420.1
OAZ3	ENST00000635322.1	c.*14+227G>C		intron_variant		5		ENSP00000489350.1

Frequencies

GnomAD3 genomes AF: 0.000125 AC: 19 AN: 151918 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.000662

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000213 AC: 75 AN: 351586 Hom.: 0 Cov.: 5 AF XY: 0.000248 AC XY: 46 AN XY: 185710

Gnomad4 AFR exome AF: 0.000114

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.000104

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00100

Gnomad4 FIN exome AF: 0.000672

Gnomad4 NFE exome AF: 0.0000758

Gnomad4 OTH exome AF: 0.0000527

GnomAD4 genome AF: 0.000125 AC: 19 AN: 151918 Hom.: 1 Cov.: 31 AF XY: 0.000202 AC XY: 15 AN XY: 74206

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000829

Gnomad4 FIN AF: 0.000662

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.2
DANN	Benign	0.78
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs1781424; hg19: chr1-151742960;