rs147813042

Variant names:

• chr8-102839749-C-A
• rs147813042
• NM_148174.4:c.177G>T

Your query was ambiguous. Multiple possible variants found:

• chr8-102839749-C-A
• chr8-102839749-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001363013.1(AZIN1):​c.-476G>T variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.000000687 in 1,456,576 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: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: AZIN1 NM_001363013.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.08
• Publications: 0 publications found

Genes affected

AZIN1 (HGNC:16432): (antizyme inhibitor 1) The protein encoded by this gene belongs to the antizyme inhibitor family, which plays a role in cell growth and proliferation by maintaining polyamine homeostasis within the cell. Antizyme inhibitors are homologs of ornithine decarboxylase (ODC, the key enzyme in polyamine biosynthesis) that have lost the ability to decarboxylase ornithine; however, retain the ability to bind to antizymes. Antizymes negatively regulate intracellular polyamine levels by binding to ODC and targeting it for degradation, as well as by inhibiting polyamine uptake. Antizyme inhibitors function as positive regulators of polyamine levels by sequestering antizymes and neutralizing their effect. This gene encodes antizyme inhibitor 1, the first member of this gene family that is ubiquitously expressed, and is localized in the nucleus and cytoplasm. Overexpression of antizyme inhibitor 1 gene has been associated with increased proliferation, cellular transformation and tumorigenesis. Gene knockout studies showed that homozygous mutant mice lacking functional antizyme inhibitor 1 gene died at birth with abnormal liver morphology. RNA editing of this gene, predominantly in the liver tissue, has been linked to the progression of hepatocellular carcinoma. Alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Sep 2014]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.19).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001363013.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AZIN1	NM_148174.4	MANE Select	c.177G>T	p.Val59Val	synonymous	Exon 4 of 12	NP_680479.1	O14977
	AZIN1	NM_001363013.1		c.-476G>T		5_prime_UTR_premature_start_codon_gain	Exon 4 of 12	NP_001349942.1
	AZIN1	NM_001363014.1		c.-476G>T		5_prime_UTR_premature_start_codon_gain	Exon 5 of 13	NP_001349943.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AZIN1	ENST00000337198.10	TSL:1 MANE Select	c.177G>T	p.Val59Val	synonymous	Exon 4 of 12	ENSP00000337180.5	O14977
	AZIN1	ENST00000347770.8	TSL:1	c.177G>T	p.Val59Val	synonymous	Exon 5 of 13	ENSP00000321507.4	O14977
	AZIN1	ENST00000682014.1		c.177G>T	p.Val59Val	synonymous	Exon 4 of 13	ENSP00000507940.1	A0A804HKI3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1456576 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 724428

African (AFR) AF: 0.00 AC: 0 AN: 33328

American (AMR) AF: 0.00 AC: 0 AN: 44162

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26038

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39544

South Asian (SAS) AF: 0.00 AC: 0 AN: 85114

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53286

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109202

Other (OTH) AF: 0.00 AC: 0 AN: 60148

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.19
CADD	Benign	7.7
DANN	Benign	0.78
PhyloP100		4.1

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: rs147813042; hg19: chr8-103851977;