Variant 3-28324421-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_022461.5(AZI2):c.800G>T(p.Gly267Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000661 in 1,528,108 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000068 ( 1 hom. )

Consequence

AZI2
NM_022461.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.340

Variant links:

Genes affected

AZI2 (HGNC:24002): (5-azacytidine induced 2) AZI2, or NAP1, contributes to the activation of NFKB (see MIM 164011)-dependent gene expression by activating IKK-related kinases, such as NAK (TBK1; MIM 604834) (Fujita et al., 2003 [PubMed 14560022]).[supplied by OMIM, Mar 2008]

AZI2 links:

CMC1 (HGNC:28783): (C-X9-C motif containing 1) Predicted to enable metal ion binding activity. Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

CMC1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.009531915).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AZI2	NM_022461.5 linkuse as main transcript	c.800G>T	p.Gly267Val	missense_variant	8/8	ENST00000479665.6
CMC1	NM_182523.2 linkuse as main transcript	c.*4792C>A		3_prime_UTR_variant	4/4	ENST00000466830.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AZI2	ENST00000479665.6 linkuse as main transcript	c.800G>T	p.Gly267Val	missense_variant	8/8	2	NM_022461.5	P1	Q9H6S1-1
CMC1	ENST00000466830.6 linkuse as main transcript	c.*4792C>A		3_prime_UTR_variant	4/4	1	NM_182523.2	P1

Frequencies

GnomAD3 genomes

AF:

0.0000463

AC:

AN:

151050

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000161

AC:

AN:

186266

Hom.:

AF XY:

0.000182

AC XY:

AN XY:

98804

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00174

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000683

AC:

AN:

1377058

Hom.:

Cov.:

AF XY:

0.0000902

AC XY:

AN XY:

676068

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00114

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000195

GnomAD4 genome

AF:

0.0000463

AC:

AN:

151050

Hom.:

Cov.:

AF XY:

0.0000678

AC XY:

AN XY:

73754

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ExAC

AF:

0.000158

AC:

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 10, 2022

The c.800G>T (p.G267V) alteration is located in exon 8 (coding exon 7) of the AZI2 gene. This alteration results from a G to T substitution at nucleotide position 800, causing the glycine (G) at amino acid position 267 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.44

Cadd

Benign

Dann

Benign

0.89

DEOGEN2

Benign

0.029

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.072

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.70

M_CAP

Benign

0.0061

MetaRNN

Benign

0.0095

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.6

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.3

REVEL

Benign

0.048

Sift

Benign

0.29

Sift4G

Benign

0.33

Polyphen

0.0030

Vest4

0.10

MutPred

0.34

Gain of glycosylation at T271 (P = 0.0154);

MVP

0.48

MPC

0.22

ClinPred

0.048

GERP RS

2.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.058

gMVP

0.25

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over