8-102839749-C-T

Position:

• chr8-102839749-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Moderate BP6_Very_Strong BS2

The NM_148174.4(AZIN1):​c.177G>A​(p.Val59Val) variant causes a synonymous change. The variant allele was found at a frequency of 0.00307 in 1,608,748 control chromosomes in the GnomAD database, including 45 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0049 (8 hom., cov: 32)
  • Exomes 𝑓: 0.0029 (37 hom.)
• Consequence: AZIN1 NM_148174.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 4.08

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

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.21).
• BP6: Variant 8-102839749-C-T is Benign according to our data. Variant chr8-102839749-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 724477.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 8 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AZIN1	NM_148174.4	c.177G>A	p.Val59Val	synonymous_variant	4/12	ENST00000337198.10	NP_680479.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AZIN1	ENST00000337198.10	c.177G>A	p.Val59Val	synonymous_variant	4/12	1	NM_148174.4	ENSP00000337180.5

Frequencies

GnomAD3 genomes AF: 0.00486 AC: 739 AN: 152098 Hom.: 8 Cov.: 32

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000589

Gnomad ASJ AF: 0.00230

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0408

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00410

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00472 AC: 1173 AN: 248456 Hom.: 10 AF XY: 0.00471 AC XY: 632 AN XY: 134320

Gnomad AFR exome AF: 0.0000621

Gnomad AMR exome AF: 0.000600

Gnomad ASJ exome AF: 0.00279

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000334

Gnomad FIN exome AF: 0.0330

Gnomad NFE exome AF: 0.00344

Gnomad OTH exome AF: 0.00365

GnomAD4 exome AF: 0.00288 AC: 4195 AN: 1456532 Hom.: 37 Cov.: 30 AF XY: 0.00295 AC XY: 2138 AN XY: 724404

Gnomad4 AFR exome AF: 0.000150

Gnomad4 AMR exome AF: 0.000611

Gnomad4 ASJ exome AF: 0.00292

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000117

Gnomad4 FIN exome AF: 0.0304

Gnomad4 NFE exome AF: 0.00211

Gnomad4 OTH exome AF: 0.00216

GnomAD4 genome AF: 0.00485 AC: 739 AN: 152216 Hom.: 8 Cov.: 32 AF XY: 0.00662 AC XY: 493 AN XY: 74420

Gnomad4 AFR AF: 0.000144

Gnomad4 AMR AF: 0.000588

Gnomad4 ASJ AF: 0.00230

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0408

Gnomad4 NFE AF: 0.00410

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00397 Hom.: 2

Bravo AF: 0.00148

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.21
CADD	Benign	8.4
DANN	Benign	0.80
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Publications

LitVar

Other links and lift over

dbSNP: rs147813042; hg19: chr8-103851977;