rs11204884

Variant names:

• chr1-151769857-G-A
• rs11204884
• ENST00000400999.7:c.480-315G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TDRKH	XM_017000123.3	c.*745C>T		3_prime_UTR_variant	Exon 14 of 14		XP_016855612.1
TDRKH	XM_047441989.1	c.*745C>T		3_prime_UTR_variant	Exon 14 of 14		XP_047297945.1
TDRKH	XM_047442008.1	c.*745C>T		3_prime_UTR_variant	Exon 14 of 14		XP_047297964.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OAZ3	ENST00000400999.7	c.480-315G>A		intron_variant	Intron 4 of 5	5		ENSP00000383784.3
OAZ3	ENST00000453029.2	c.384-315G>A		intron_variant	Intron 4 of 5	5		ENSP00000415904.2
OAZ3	ENST00000321531.10	c.345-315G>A		intron_variant	Intron 4 of 5	5		ENSP00000313922.5
OAZ3	ENST00000479764.7	c.304-315G>A		intron_variant	Intron 3 of 4	5		ENSP00000463055.3
OAZ3	ENST00000635374.1	c.282-1220G>A		intron_variant	Intron 3 of 3	5		ENSP00000489420.1
OAZ3	ENST00000635322.1	c.169-315G>A		intron_variant	Intron 3 of 4	5		ENSP00000489350.1

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

African (AFR) AF: 0.184 AC: 7661 AN: 41532

American (AMR) AF: 0.135 AC: 2068 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0919 AC: 319 AN: 3472

East Asian (EAS) AF: 0.115 AC: 594 AN: 5170

South Asian (SAS) AF: 0.101 AC: 486 AN: 4826

European-Finnish (FIN) AF: 0.167 AC: 1773 AN: 10610

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.148 AC: 10052 AN: 68016

Other (OTH) AF: 0.134 AC: 282 AN: 2110

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
PhyloP100		0.089
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11204884; hg19: chr1-151742333;