1-151770322-T-G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000525790.5(TDRKH):​n.*1443A>C 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 0.00000641 in 1,403,246 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000064 (0 hom.)
• Consequence: TDRKH ENST00000525790.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.101
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).

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+65T>G		intron	N/A	NP_057262.2
	OAZ3	NM_001301371.1		c.469+65T>G		intron	N/A	NP_001288300.1
	OAZ3	NM_001134939.1		c.430+65T>G		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.*1443A>C		non_coding_transcript_exon	Exon 14 of 14	ENSP00000437147.1
	TDRKH	ENST00000525790.5	TSL:1	n.*1443A>C		3_prime_UTR	Exon 14 of 14	ENSP00000437147.1
	OAZ3	ENST00000400999.7	TSL:5	c.565+65T>G		intron	N/A	ENSP00000383784.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000641 AC: 9 AN: 1403246 Hom.: 0 Cov.: 31 AF XY: 0.0000130 AC XY: 9 AN XY: 693626

African (AFR) AF: 0.00 AC: 0 AN: 31530

American (AMR) AF: 0.00 AC: 0 AN: 37830

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22286

East Asian (EAS) AF: 0.00 AC: 0 AN: 38488

South Asian (SAS) AF: 0.000117 AC: 9 AN: 77250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50026

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5440

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1082790

Other (OTH) AF: 0.00 AC: 0 AN: 57606

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	10
DANN	Benign	0.79
PhyloP100		0.10

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: rs3748612; hg19: chr1-151742798;