rs1781424

Variant names:

• chr1-151770484-G-A
• rs1781424
• ENST00000525790.5:n.*1281C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-151770484-G-A
• chr1-151770484-G-C
• chr1-151770484-G-T

Variant summary

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

The ENST00000525790.5(TDRKH):​n.*1281C>T 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 0.448 in 502,180 control chromosomes in the GnomAD database, including 53,245 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 (13777 hom., cov: 31)
  • Exomes 𝑓: 0.47 (39468 hom.)
• Consequence: TDRKH ENST00000525790.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.569
• Publications: 5 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.508 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000525790.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OAZ3	NM_016178.2		c.565+227G>A		intron	N/A	NP_057262.2
	OAZ3	NM_001301371.1		c.469+227G>A		intron	N/A	NP_001288300.1
	OAZ3	NM_001134939.1		c.430+227G>A		intron	N/A	NP_001128411.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TDRKH	ENST00000525790.5	TSL:1	n.*1281C>T		non_coding_transcript_exon	Exon 14 of 14	ENSP00000437147.1
	TDRKH	ENST00000525790.5	TSL:1	n.*1281C>T		3_prime_UTR	Exon 14 of 14	ENSP00000437147.1
	OAZ3	ENST00000400999.7	TSL:5	c.565+227G>A		intron	N/A	ENSP00000383784.3

Frequencies

GnomAD3 genomes AF: 0.409 AC: 62168 AN: 151848 Hom.: 13778 Cov.: 31

Gnomad AFR AF: 0.273

Gnomad AMI AF: 0.572

Gnomad AMR AF: 0.334

Gnomad ASJ AF: 0.394

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.409

Gnomad FIN AF: 0.469

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.513

Gnomad OTH AF: 0.404

GnomAD4 exome AF: 0.465 AC: 162858 AN: 350214 Hom.: 39468 Cov.: 5 AF XY: 0.460 AC XY: 85137 AN XY: 185030

African (AFR) AF: 0.263 AC: 2294 AN: 8722

American (AMR) AF: 0.306 AC: 3300 AN: 10782

Ashkenazi Jewish (ASJ) AF: 0.407 AC: 3886 AN: 9552

East Asian (EAS) AF: 0.241 AC: 4420 AN: 18348

South Asian (SAS) AF: 0.399 AC: 15890 AN: 39794

European-Finnish (FIN) AF: 0.474 AC: 9143 AN: 19278

Middle Eastern (MID) AF: 0.431 AC: 630 AN: 1462

European-Non Finnish (NFE) AF: 0.515 AC: 114935 AN: 223378

Other (OTH) AF: 0.442 AC: 8360 AN: 18898

GnomAD4 genome AF: 0.409 AC: 62167 AN: 151966 Hom.: 13777 Cov.: 31 AF XY: 0.403 AC XY: 29943 AN XY: 74300

African (AFR) AF: 0.273 AC: 11306 AN: 41414

American (AMR) AF: 0.334 AC: 5096 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.394 AC: 1366 AN: 3468

East Asian (EAS) AF: 0.221 AC: 1141 AN: 5168

South Asian (SAS) AF: 0.409 AC: 1970 AN: 4818

European-Finnish (FIN) AF: 0.469 AC: 4958 AN: 10570

Middle Eastern (MID) AF: 0.411 AC: 120 AN: 292

European-Non Finnish (NFE) AF: 0.513 AC: 34836 AN: 67944

Other (OTH) AF: 0.405 AC: 852 AN: 2102

Alfa AF: 0.419 Hom.: 2467

Bravo AF: 0.392

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.5
DANN	Benign	0.73
PhyloP100		-0.57
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: rs1781424; hg19: chr1-151742960; COSMIC: COSV58619376; COSMIC: COSV58619376;