rs4995159

Variant names:

• chr1-151770018-A-G
• rs4995159
• ENST00000400999.7:c.480-154A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000400999.7(OAZ3):​c.480-154A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.499 in 1,282,842 control chromosomes in the GnomAD database, including 163,823 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 0.42 (14073 hom., cov: 33)
  • Exomes 𝑓: 0.51 (149750 hom.)
• Consequence: OAZ3 ENST00000400999.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.89
• Publications: 2 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=-1.03).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.509 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TDRKH	XM_017000123.3	c.*584T>C		3_prime_UTR_variant	Exon 14 of 14		XP_016855612.1
TDRKH	XM_047441989.1	c.*584T>C		3_prime_UTR_variant	Exon 14 of 14		XP_047297945.1
TDRKH	XM_047442008.1	c.*584T>C		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.480-154A>G		intron_variant	Intron 4 of 5	5		ENSP00000383784.3
OAZ3	ENST00000453029.2	c.384-154A>G		intron_variant	Intron 4 of 5	5		ENSP00000415904.2
OAZ3	ENST00000321531.10	c.345-154A>G		intron_variant	Intron 4 of 5	5		ENSP00000313922.5
OAZ3	ENST00000479764.7	c.304-154A>G		intron_variant	Intron 3 of 4	5		ENSP00000463055.3
OAZ3	ENST00000635374.1	c.282-1059A>G		intron_variant	Intron 3 of 3	5		ENSP00000489420.1
OAZ3	ENST00000635322.1	c.169-154A>G		intron_variant	Intron 3 of 4	5		ENSP00000489350.1

Frequencies

GnomAD3 genomes AF: 0.415 AC: 63136 AN: 151962 Hom.: 14072 Cov.: 33

Gnomad AFR AF: 0.294

Gnomad AMI AF: 0.574

Gnomad AMR AF: 0.336

Gnomad ASJ AF: 0.395

Gnomad EAS AF: 0.222

Gnomad SAS AF: 0.410

Gnomad FIN AF: 0.470

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.513

Gnomad OTH AF: 0.409

GnomAD4 exome AF: 0.511 AC: 577581 AN: 1130762 Hom.: 149750 AF XY: 0.508 AC XY: 290784 AN XY: 572830

African (AFR) AF: 0.308 AC: 7920 AN: 25714

American (AMR) AF: 0.296 AC: 11329 AN: 38210

Ashkenazi Jewish (ASJ) AF: 0.431 AC: 8892 AN: 20624

East Asian (EAS) AF: 0.253 AC: 8210 AN: 32454

South Asian (SAS) AF: 0.421 AC: 31524 AN: 74842

European-Finnish (FIN) AF: 0.507 AC: 19986 AN: 39442

Middle Eastern (MID) AF: 0.458 AC: 1913 AN: 4174

European-Non Finnish (NFE) AF: 0.549 AC: 465477 AN: 848218

Other (OTH) AF: 0.474 AC: 22330 AN: 47084

GnomAD4 genome AF: 0.415 AC: 63137 AN: 152080 Hom.: 14073 Cov.: 33 AF XY: 0.410 AC XY: 30445 AN XY: 74338

African (AFR) AF: 0.293 AC: 12172 AN: 41490

American (AMR) AF: 0.335 AC: 5131 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.395 AC: 1369 AN: 3470

East Asian (EAS) AF: 0.221 AC: 1140 AN: 5152

South Asian (SAS) AF: 0.410 AC: 1976 AN: 4822

European-Finnish (FIN) AF: 0.470 AC: 4969 AN: 10572

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.513 AC: 34873 AN: 67972

Other (OTH) AF: 0.410 AC: 863 AN: 2104

Alfa AF: 0.472 Hom.: 2137

Bravo AF: 0.399

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.3
DANN	Benign	0.17
PhyloP100		-1.9
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: rs4995159; hg19: chr1-151742494;