ENST00000525790.5:n.*1203-833delT

Variant names:

• chr1-151771394-TA-T
• rs3833528
• ENST00000525790.5:n.*1203-833delT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The ENST00000525790.5(TDRKH):​n.*1203-833delT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.41 (13808 hom., cov: 0)
  • Exomes 𝑓: 0.49 (145765 hom.)
• Consequence: TDRKH ENST00000525790.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0670
• Publications: 3 publications found

Genes affected

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]

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]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• 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
TDRKH	XM_017000123.3	c.*40-833delT		intron_variant	Intron 13 of 13		XP_016855612.1
TDRKH	XM_047441989.1	c.*40-833delT		intron_variant	Intron 13 of 13		XP_047297945.1
TDRKH	XM_047442008.1	c.*40-833delT		intron_variant	Intron 13 of 13		XP_047297964.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OAZ3	ENST00000400999.7	c.*176delA		downstream_gene_variant		5		ENSP00000383784.3
OAZ3	ENST00000453029.2	c.*176delA		downstream_gene_variant		5		ENSP00000415904.2
OAZ3	ENST00000321531.10	c.*176delA		downstream_gene_variant		5		ENSP00000313922.5
OAZ3	ENST00000479764.7	c.*333delA		downstream_gene_variant		5		ENSP00000463055.3
OAZ3	ENST00000635374.1	c.*282delA		downstream_gene_variant		5		ENSP00000489420.1
OAZ3	ENST00000635322.1	c.*333delA		downstream_gene_variant		5		ENSP00000489350.1

Frequencies

GnomAD3 genomes AF: 0.410 AC: 62268 AN: 151866 Hom.: 13809 Cov.: 0

Gnomad AFR AF: 0.276

Gnomad AMI AF: 0.571

Gnomad AMR AF: 0.334

Gnomad ASJ AF: 0.394

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.410

Gnomad FIN AF: 0.468

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.513

Gnomad OTH AF: 0.404

GnomAD4 exome AF: 0.490 AC: 583051 AN: 1190756 Hom.: 145765 Cov.: 0 AF XY: 0.488 AC XY: 281328 AN XY: 576552

African (AFR) AF: 0.259 AC: 6453 AN: 24918

American (AMR) AF: 0.304 AC: 3944 AN: 12966

Ashkenazi Jewish (ASJ) AF: 0.411 AC: 7143 AN: 17390

East Asian (EAS) AF: 0.244 AC: 7274 AN: 29860

South Asian (SAS) AF: 0.405 AC: 20970 AN: 51744

European-Finnish (FIN) AF: 0.472 AC: 15220 AN: 32272

Middle Eastern (MID) AF: 0.421 AC: 1421 AN: 3378

European-Non Finnish (NFE) AF: 0.515 AC: 498386 AN: 968572

Other (OTH) AF: 0.448 AC: 22240 AN: 49656

GnomAD4 genome AF: 0.410 AC: 62268 AN: 151984 Hom.: 13808 Cov.: 0 AF XY: 0.404 AC XY: 29989 AN XY: 74296

African (AFR) AF: 0.275 AC: 11407 AN: 41450

American (AMR) AF: 0.333 AC: 5086 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.394 AC: 1369 AN: 3472

East Asian (EAS) AF: 0.221 AC: 1141 AN: 5166

South Asian (SAS) AF: 0.410 AC: 1979 AN: 4822

European-Finnish (FIN) AF: 0.468 AC: 4938 AN: 10554

Middle Eastern (MID) AF: 0.414 AC: 121 AN: 292

European-Non Finnish (NFE) AF: 0.513 AC: 34852 AN: 67946

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

Alfa AF: 0.469 Hom.: 2114

Bravo AF: 0.393

Asia WGS AF: 0.345 AC: 1200 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.067
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3833528; hg19: chr1-151743870;