Variant 1-33096815-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_052998.4(AZIN2):c.862G>T(p.Ala288Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00692 in 1,614,204 control chromosomes in the GnomAD database, including 567 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.011 ( 73 hom., cov: 32)

Exomes 𝑓: 0.0065 ( 494 hom. )

Consequence

AZIN2
NM_052998.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 10.0

Variant links:

Genes affected

AZIN2 (HGNC:29957): (antizyme inhibitor 2) 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 2, the second member of this gene family. Like antizyme inhibitor 1, antizyme inhibitor 2 interacts with all 3 antizymes and stimulates ODC activity and polyamine uptake. However, unlike antizyme inhibitor 1, which is ubiquitously expressed and localized in the nucleus and cytoplasm, antizyme inhibitor 2 is predominantly expressed in the brain and testis and localized in the endoplasmic reticulum-golgi intermediate compartment. Recent studies indicate that antizyme inhibitor 2 is also expressed in specific cell types in ovaries, adrenal glands and pancreas, and in mast cells. The exact function of this gene is not known, however, available data suggest its role in cell growth, spermiogenesis, vesicular trafficking and secretion. Accumulation of antizyme inhibitor 2 has also been observed in brains of patients with Alzheimer's disease. There has been confusion in literature and databases over the nomenclature of this gene, stemming from an earlier report that a human cDNA clone (identical to ODCp/AZIN2) had arginine decarboxylase (ADC) activity (PMID:14738999). Subsequent studies in human and mouse showed that antizyme inhibitor 2 was devoid of arginine decarboxylase activity (PMID:19956990). Alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Sep 2014]

AZIN2 links:

AZIN2 (HGNC:):

AZIN2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0024927258).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0924 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AZIN2	NM_052998.4 linkuse as main transcript	c.862G>T	p.Ala288Ser	missense_variant	9/12	ENST00000294517.11	NP_443724.1	Q96A70-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AZIN2	ENST00000294517.11 linkuse as main transcript	c.862G>T	p.Ala288Ser	missense_variant	9/12	1	NM_052998.4	ENSP00000294517.6		Q96A70-1

Frequencies

GnomAD3 genomes

AF:

0.0111

AC:

1688

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00152

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0639

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.0998

Gnomad SAS

AF:

0.00745

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000720

Gnomad OTH

AF:

0.0167

GnomAD3 exomes

AF:

0.0249

AC:

6251

AN:

251436

Hom.:

393

AF XY:

0.0199

AC XY:

2705

AN XY:

135888

show subpopulations

Gnomad AFR exome

AF:

0.000738

Gnomad AMR exome

AF:

0.118

Gnomad ASJ exome

AF:

0.00188

Gnomad EAS exome

AF:

0.0992

Gnomad SAS exome

AF:

0.00317

Gnomad FIN exome

AF:

0.000231

Gnomad NFE exome

AF:

0.000791

Gnomad OTH exome

AF:

0.0184

GnomAD4 exome

AF:

0.00649

AC:

9494

AN:

1461892

Hom.:

494

Cov.:

AF XY:

0.00587

AC XY:

4272

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.000627

Gnomad4 AMR exome

AF:

0.111

Gnomad4 ASJ exome

AF:

0.00226

Gnomad4 EAS exome

AF:

0.0791

Gnomad4 SAS exome

AF:

0.00380

Gnomad4 FIN exome

AF:

0.000300

Gnomad4 NFE exome

AF:

0.000351

Gnomad4 OTH exome

AF:

0.00979

GnomAD4 genome

AF:

0.0110

AC:

1682

AN:

152312

Hom.:

Cov.:

AF XY:

0.0122

AC XY:

909

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.00152

Gnomad4 AMR

AF:

0.0635

Gnomad4 ASJ

AF:

0.00317

Gnomad4 EAS

AF:

0.0995

Gnomad4 SAS

AF:

0.00746

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000720

Gnomad4 OTH

AF:

0.0170

Alfa

AF:

0.00497

Hom.:

Bravo

AF:

0.0174

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.000930

AC:

ExAC

AF:

0.0204

AC:

2475

Asia WGS

AF:

0.0400

AC:

139

AN:

3478

EpiCase

AF:

0.000545

EpiControl

AF:

0.000711

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.23

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.53

D;D;.;.

Eigen

Uncertain

0.68

Eigen_PC

Pathogenic

0.72

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.91

.;D;D;D

MetaRNN

Benign

0.0025

T;T;T;T

MetaSVM

Benign

-0.84

PrimateAI

Benign

0.47

PROVEAN

Uncertain

-2.8

D;D;D;D

REVEL

Uncertain

0.39

Sift

Uncertain

0.0020

D;D;D;D

Sift4G

Uncertain

0.0020

D;D;D;D

Polyphen

0.28

B;B;D;P

Vest4

0.44

MPC

0.40

ClinPred

0.060

GERP RS

5.7

Varity_R

0.61

gMVP

0.40

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over