chr3-28338602-A-G

Position:

• chr3-28338602-A-G

Variant summary

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

The NM_022461.5(AZI2):​c.230T>C​(p.Phe77Ser) 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 (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: AZI2 NM_022461.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.593

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=0.07147935).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AZI2	NM_022461.5	c.230T>C	p.Phe77Ser	missense_variant	3/8	ENST00000479665.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AZI2	ENST00000479665.6	c.230T>C	p.Phe77Ser	missense_variant	3/8	2	NM_022461.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 18, 2023

The c.230T>C (p.F77S) alteration is located in exon 3 (coding exon 2) of the AZI2 gene. This alteration results from a T to C substitution at nucleotide position 230, causing the phenylalanine (F) at amino acid position 77 to be replaced by a serine (S). 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	0.056
BayesDel_addAF	Benign	-0.094	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	12
DANN	Uncertain	0.98
DEOGEN2	Benign	0.32	T;.;.;.;T;T
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.076	N
LIST_S2	Benign	0.51	T;T;.;T;T;T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.071	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L;L;L;L;.;.
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-3.5	D;D;D;D;D;D
REVEL	Benign	0.049
Sift	Benign	0.045	D;D;D;D;D;D
Sift4G	Benign	0.33	T;T;T;T;.;.
Polyphen		0.0010	B;.;.;.;B;B
Vest4		0.13
MutPred		0.33		Gain of disorder (P = 0.0175);Gain of disorder (P = 0.0175);Gain of disorder (P = 0.0175);Gain of disorder (P = 0.0175);Gain of disorder (P = 0.0175);Gain of disorder (P = 0.0175);
MVP		0.26
MPC		0.30
ClinPred		0.16	T
GERP RS		0.65
Varity_R		0.17
gMVP		0.37

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-28380093;