chr1-151770078-A-G

Variant names:

• chr1-151770078-A-G
• rs4995158
• ENST00000400999.7:c.480-94A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_016178.2(OAZ3):​c.480-94A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.00059 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0011 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: OAZ3 NM_016178.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.78
• Publications: 1 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016178.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OAZ3	NM_016178.2		c.480-94A>G		intron	N/A	NP_057262.2
	OAZ3	NM_001301371.1		c.384-94A>G		intron	N/A	NP_001288300.1
	OAZ3	NM_001134939.1		c.345-94A>G		intron	N/A	NP_001128411.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OAZ3	ENST00000400999.7	TSL:5	c.480-94A>G		intron	N/A	ENSP00000383784.3
	OAZ3	ENST00000453029.2	TSL:5	c.384-94A>G		intron	N/A	ENSP00000415904.2
	OAZ3	ENST00000321531.10	TSL:5	c.345-94A>G		intron	N/A	ENSP00000313922.5

Frequencies

GnomAD3 genomes AF: 0.000592 AC: 32 AN: 54088 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000290

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000441

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00285

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000853

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00111 AC: 439 AN: 395554 Hom.: 1 Cov.: 0 AF XY: 0.00107 AC XY: 211 AN XY: 197992

African (AFR) AF: 0.000296 AC: 5 AN: 16898

American (AMR) AF: 0.000432 AC: 10 AN: 23166

Ashkenazi Jewish (ASJ) AF: 0.000445 AC: 4 AN: 8986

East Asian (EAS) AF: 0.00213 AC: 47 AN: 22090

South Asian (SAS) AF: 0.000324 AC: 10 AN: 30856

European-Finnish (FIN) AF: 0.000429 AC: 6 AN: 13996

Middle Eastern (MID) AF: 0.00102 AC: 2 AN: 1962

European-Non Finnish (NFE) AF: 0.00129 AC: 335 AN: 259456

Other (OTH) AF: 0.00110 AC: 20 AN: 18144

GnomAD4 genome AF: 0.000590 AC: 32 AN: 54206 Hom.: 0 Cov.: 0 AF XY: 0.000703 AC XY: 19 AN XY: 27012

African (AFR) AF: 0.000289 AC: 6 AN: 20770

American (AMR) AF: 0.000439 AC: 3 AN: 6830

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1288

East Asian (EAS) AF: 0.00285 AC: 9 AN: 3158

South Asian (SAS) AF: 0.00 AC: 0 AN: 1698

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3026

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 106

European-Non Finnish (NFE) AF: 0.000853 AC: 14 AN: 16408

Other (OTH) AF: 0.00 AC: 0 AN: 750

Alfa AF: 0.0529 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	4.0
DANN	Benign	0.073
PhyloP100		-1.8
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: rs4995158; hg19: chr1-151742554; COSMIC: COSV58617566; COSMIC: COSV58617566;