rs11204884

chr1-151769857-G-A

Variant summary

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

The ENST00000400999.7(OAZ3):c.480-315G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 152,238 control chromosomes in the GnomAD database, including 1,893 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 0.15 (1893 hom., cov: 32)
• Consequence: OAZ3 ENST00000400999.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0890

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OAZ3	NM_001134939.1	c.346-315G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OAZ3	ENST00000400999.7	c.480-315G>A		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23427 AN: 152120 Hom.: 1887 Cov.: 32

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.218

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.0919

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.167

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.136

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.154 AC: 23456 AN: 152238 Hom.: 1893 Cov.: 32 AF XY: 0.153 AC XY: 11351 AN XY: 74428

Gnomad4 AFR AF: 0.184

Gnomad4 AMR AF: 0.135

Gnomad4 ASJ AF: 0.0919

Gnomad4 EAS AF: 0.115

Gnomad4 SAS AF: 0.101

Gnomad4 FIN AF: 0.167

Gnomad4 NFE AF: 0.148

Gnomad4 OTH AF: 0.134

Alfa AF: 0.146 Hom.: 201

Bravo AF: 0.156

Asia WGS AF: 0.127 AC: 441 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	5.1
Dann	Benign	0.61

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: rs11204884; hg19: chr1-151742333;