rs1781420

Variant names:

• chr1-151770888-C-A
• rs1781420
• ENST00000400999.7:c.566-189C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-151770888-C-A
• chr1-151770888-C-T

Variant summary

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

The ENST00000400999.7(OAZ3):​c.566-189C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 152,084 control chromosomes in the GnomAD database, including 13,768 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 0.41 (13768 hom., cov: 32)
• Consequence: OAZ3 ENST00000400999.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.513
• Publications: 5 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.508 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OAZ3	NM_016178.2	c.566-189C>A		intron_variant	Intron 4 of 4		NP_057262.2
OAZ3	NM_001301371.1	c.470-189C>A		intron_variant	Intron 4 of 4		NP_001288300.1
OAZ3	NM_001134939.1	c.431-189C>A		intron_variant	Intron 4 of 4		NP_001128411.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OAZ3	ENST00000400999.7	c.566-189C>A		intron_variant	Intron 5 of 5	5		ENSP00000383784.3
OAZ3	ENST00000453029.2	c.470-189C>A		intron_variant	Intron 5 of 5	5		ENSP00000415904.2
OAZ3	ENST00000321531.10	c.431-189C>A		intron_variant	Intron 5 of 5	5		ENSP00000313922.5
OAZ3	ENST00000479764.7	c.*15-189C>A		intron_variant	Intron 4 of 4	5		ENSP00000463055.3
OAZ3	ENST00000635374.1	c.282-189C>A		intron_variant	Intron 3 of 3	5		ENSP00000489420.1
OAZ3	ENST00000635322.1	c.*15-189C>A		intron_variant	Intron 4 of 4	5		ENSP00000489350.1

Frequencies

GnomAD3 genomes AF: 0.409 AC: 62098 AN: 151966 Hom.: 13769 Cov.: 32

Gnomad AFR AF: 0.273

Gnomad AMI AF: 0.575

Gnomad AMR AF: 0.333

Gnomad ASJ AF: 0.394

Gnomad EAS AF: 0.207

Gnomad SAS AF: 0.406

Gnomad FIN AF: 0.470

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.513

Gnomad OTH AF: 0.404

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

GnomAD4 genome AF: 0.408 AC: 62098 AN: 152084 Hom.: 13768 Cov.: 32 AF XY: 0.402 AC XY: 29907 AN XY: 74326

African (AFR) AF: 0.273 AC: 11313 AN: 41494

American (AMR) AF: 0.332 AC: 5082 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.394 AC: 1367 AN: 3468

East Asian (EAS) AF: 0.206 AC: 1068 AN: 5174

South Asian (SAS) AF: 0.406 AC: 1954 AN: 4808

European-Finnish (FIN) AF: 0.470 AC: 4960 AN: 10562

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

European-Non Finnish (NFE) AF: 0.513 AC: 34856 AN: 67970

Other (OTH) AF: 0.405 AC: 855 AN: 2110

Alfa AF: 0.334 Hom.: 957

Bravo AF: 0.391

Asia WGS AF: 0.320 AC: 1116 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.5
DANN	Benign	0.66
PhyloP100		0.51
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: rs1781420; hg19: chr1-151743364; COSMIC: COSV58620147; COSMIC: COSV58620147;