ENST00000525790.5:n.*1443A>G

Variant names:

• chr1-151770322-T-C
• rs3748612
• ENST00000525790.5:n.*1443A>G

Variant summary

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

The ENST00000525790.5(TDRKH):​n.*1443A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 1,553,996 control chromosomes in the GnomAD database, including 83,541 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 0.32 (8010 hom., cov: 31)
  • Exomes 𝑓: 0.33 (75531 hom.)
• Consequence: TDRKH ENST00000525790.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.101
• Publications: 7 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.383 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TDRKH	XM_017000123.3	c.*280A>G		3_prime_UTR_variant	Exon 14 of 14		XP_016855612.1
TDRKH	XM_047441989.1	c.*280A>G		3_prime_UTR_variant	Exon 14 of 14		XP_047297945.1
TDRKH	XM_047442008.1	c.*280A>G		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.565+65T>C		intron_variant	Intron 5 of 5	5		ENSP00000383784.3
OAZ3	ENST00000453029.2	c.469+65T>C		intron_variant	Intron 5 of 5	5		ENSP00000415904.2
OAZ3	ENST00000321531.10	c.430+65T>C		intron_variant	Intron 5 of 5	5		ENSP00000313922.5
OAZ3	ENST00000479764.7	c.*14+65T>C		intron_variant	Intron 4 of 4	5		ENSP00000463055.3
OAZ3	ENST00000635374.1	c.282-755T>C		intron_variant	Intron 3 of 3	5		ENSP00000489420.1
OAZ3	ENST00000635322.1	c.*14+65T>C		intron_variant	Intron 4 of 4	5		ENSP00000489350.1

Frequencies

GnomAD3 genomes AF: 0.317 AC: 48083 AN: 151864 Hom.: 7996 Cov.: 31

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.391

Gnomad ASJ AF: 0.502

Gnomad EAS AF: 0.270

Gnomad SAS AF: 0.255

Gnomad FIN AF: 0.361

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.352

GnomAD4 exome AF: 0.326 AC: 456513 AN: 1402014 Hom.: 75531 Cov.: 31 AF XY: 0.326 AC XY: 225924 AN XY: 693018

African (AFR) AF: 0.245 AC: 7725 AN: 31494

American (AMR) AF: 0.365 AC: 13799 AN: 37772

Ashkenazi Jewish (ASJ) AF: 0.485 AC: 10800 AN: 22252

East Asian (EAS) AF: 0.285 AC: 10967 AN: 38452

South Asian (SAS) AF: 0.278 AC: 21489 AN: 77202

European-Finnish (FIN) AF: 0.358 AC: 17888 AN: 49948

Middle Eastern (MID) AF: 0.459 AC: 2495 AN: 5432

European-Non Finnish (NFE) AF: 0.325 AC: 351903 AN: 1081928

Other (OTH) AF: 0.338 AC: 19447 AN: 57534

GnomAD4 genome AF: 0.317 AC: 48141 AN: 151982 Hom.: 8010 Cov.: 31 AF XY: 0.319 AC XY: 23728 AN XY: 74280

African (AFR) AF: 0.248 AC: 10268 AN: 41474

American (AMR) AF: 0.392 AC: 5983 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.502 AC: 1739 AN: 3464

East Asian (EAS) AF: 0.270 AC: 1394 AN: 5156

South Asian (SAS) AF: 0.256 AC: 1232 AN: 4814

European-Finnish (FIN) AF: 0.361 AC: 3813 AN: 10552

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.333 AC: 22642 AN: 67928

Other (OTH) AF: 0.354 AC: 747 AN: 2110

Alfa AF: 0.326 Hom.: 3329

Bravo AF: 0.312

Asia WGS AF: 0.262 AC: 912 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	12
DANN	Benign	0.77
PhyloP100		0.10
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs3748612; hg19: chr1-151742798; COSMIC: COSV58617267; COSMIC: COSV58617267;