3-28337952-C-T

Position:

• chr3-28337952-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_022461.5(AZI2):​c.424G>A​(p.Val142Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V142A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: AZI2 NM_022461.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.92

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19129917).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AZI2	NM_022461.5	c.424G>A	p.Val142Met	missense_variant	4/8	ENST00000479665.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AZI2	ENST00000479665.6	c.424G>A	p.Val142Met	missense_variant	4/8	2	NM_022461.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.056	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	23
DANN	Benign	0.95
DEOGEN2	Benign	0.034	T;.;.;.;T
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.89	D;D;.;D;D
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.19	T;T;T;T;T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	0.88	L;L;L;L;.
MutationTaster	Benign	0.94	D;D;D;D
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	0.020	N;N;N;N;N
REVEL	Benign	0.089
Sift	Benign	0.25	T;T;T;T;T
Sift4G	Benign	0.35	T;T;T;T;.
Polyphen		0.085	B;.;.;.;P
Vest4		0.30
MutPred		0.34		Gain of glycosylation at T140 (P = 0.0436);Gain of glycosylation at T140 (P = 0.0436);Gain of glycosylation at T140 (P = 0.0436);Gain of glycosylation at T140 (P = 0.0436);Gain of glycosylation at T140 (P = 0.0436);
MVP		0.32
MPC		0.23
ClinPred		0.52	D
GERP RS		5.8
Varity_R		0.15
gMVP		0.15

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: rs767489266; hg19: chr3-28379443;