chr1-151770322-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).

Transcripts

RefSeq

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

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 v4.3

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;