chr8-102839749-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId is 724477.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 8 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_148174.4. 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>A	p.Val59Val	synonymous	Exon 4 of 12	NP_680479.1	O14977
	AZIN1	NM_001363024.1		c.177G>A	p.Val59Val	synonymous	Exon 5 of 13	NP_001349953.1	O14977
	AZIN1	NM_001363083.1		c.177G>A	p.Val59Val	synonymous	Exon 5 of 13	NP_001350012.1	O14977

Ensembl Transcripts

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

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

GnomAD2 exomes AF: 0.00472 AC: 1173 AN: 248456 AF XY: 0.00471

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 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

African (AFR) AF: 0.000150 AC: 5 AN: 33328

American (AMR) AF: 0.000611 AC: 27 AN: 44160

Ashkenazi Jewish (ASJ) AF: 0.00292 AC: 76 AN: 26038

East Asian (EAS) AF: 0.00 AC: 0 AN: 39544

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85114

European-Finnish (FIN) AF: 0.0304 AC: 1618 AN: 53276

Middle Eastern (MID) AF: 0.000348 AC: 2 AN: 5754

European-Non Finnish (NFE) AF: 0.00211 AC: 2336 AN: 1109172

Other (OTH) AF: 0.00216 AC: 130 AN: 60146

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

African (AFR) AF: 0.000144 AC: 6 AN: 41540

American (AMR) AF: 0.000588 AC: 9 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00230 AC: 8 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.0408 AC: 432 AN: 10588

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00410 AC: 279 AN: 68002

Other (OTH) AF: 0.00237 AC: 5 AN: 2112

Alfa AF: 0.00397 Hom.: 2

Bravo AF: 0.00148

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.21
CADD	Benign	8.4
DANN	Benign	0.80
PhyloP100		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=59/41	polymorphism

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;