chr1-151767944-G-A

Variant names:

• chr1-151767944-G-A
• rs12066445
• ENST00000400999.7:c.304-114G>A

Variant summary

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

The ENST00000400999.7(OAZ3):​c.304-114G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 1,323,092 control chromosomes in the GnomAD database, including 69,368 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 0.30 (7498 hom., cov: 32)
  • Exomes 𝑓: 0.32 (61870 hom.)
• Consequence: OAZ3 ENST00000400999.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.369
• Publications: 16 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]

ENSG00000249602 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.377 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TDRKH	XM_017000123.3	c.*2658C>T		3_prime_UTR_variant	Exon 14 of 14		XP_016855612.1
TDRKH	XM_047441989.1	c.*2658C>T		3_prime_UTR_variant	Exon 14 of 14		XP_047297945.1
TDRKH	XM_047442008.1	c.*2658C>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.304-114G>A		intron_variant	Intron 3 of 5	5		ENSP00000383784.3
OAZ3	ENST00000453029.2	c.208-114G>A		intron_variant	Intron 3 of 5	5		ENSP00000415904.2
OAZ3	ENST00000321531.10	c.169-114G>A		intron_variant	Intron 3 of 5	5		ENSP00000313922.5
OAZ3	ENST00000479764.7	c.303+645G>A		intron_variant	Intron 3 of 4	5		ENSP00000463055.3
OAZ3	ENST00000635374.1	c.106-114G>A		intron_variant	Intron 2 of 3	5		ENSP00000489420.1
OAZ3	ENST00000635322.1	c.168+645G>A		intron_variant	Intron 3 of 4	5		ENSP00000489350.1

Frequencies

GnomAD3 genomes AF: 0.303 AC: 46047 AN: 151896 Hom.: 7488 Cov.: 32

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.210

Gnomad AMR AF: 0.384

Gnomad ASJ AF: 0.482

Gnomad EAS AF: 0.256

Gnomad SAS AF: 0.255

Gnomad FIN AF: 0.362

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.332

Gnomad OTH AF: 0.339

GnomAD4 exome AF: 0.322 AC: 376546 AN: 1171080 Hom.: 61870 Cov.: 16 AF XY: 0.322 AC XY: 186760 AN XY: 579930

African (AFR) AF: 0.199 AC: 5388 AN: 27018

American (AMR) AF: 0.363 AC: 10053 AN: 27666

Ashkenazi Jewish (ASJ) AF: 0.462 AC: 8967 AN: 19410

East Asian (EAS) AF: 0.276 AC: 9936 AN: 36014

South Asian (SAS) AF: 0.277 AC: 18036 AN: 65044

European-Finnish (FIN) AF: 0.358 AC: 16660 AN: 46506

Middle Eastern (MID) AF: 0.439 AC: 1496 AN: 3406

European-Non Finnish (NFE) AF: 0.323 AC: 289645 AN: 896244

Other (OTH) AF: 0.329 AC: 16365 AN: 49772

GnomAD4 genome AF: 0.303 AC: 46087 AN: 152012 Hom.: 7498 Cov.: 32 AF XY: 0.306 AC XY: 22761 AN XY: 74276

African (AFR) AF: 0.206 AC: 8529 AN: 41476

American (AMR) AF: 0.385 AC: 5882 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.482 AC: 1673 AN: 3472

East Asian (EAS) AF: 0.257 AC: 1328 AN: 5170

South Asian (SAS) AF: 0.256 AC: 1235 AN: 4828

European-Finnish (FIN) AF: 0.362 AC: 3814 AN: 10536

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.332 AC: 22590 AN: 67940

Other (OTH) AF: 0.341 AC: 717 AN: 2104

Alfa AF: 0.323 Hom.: 7526

Bravo AF: 0.296

Asia WGS AF: 0.246 AC: 859 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.8
DANN	Benign	0.67
PhyloP100		0.37
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs12066445; hg19: chr1-151740420; COSMIC: COSV58617295; COSMIC: COSV58617295;