19-830781-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001700.5(AZU1):​c.434C>A​(p.Ala145Asp) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

AZU1
NM_001700.5 missense

Scores

1
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0810
Variant links:
Genes affected
AZU1 (HGNC:913): (azurocidin 1) Azurophil granules, specialized lysosomes of the neutrophil, contain at least 10 proteins implicated in the killing of microorganisms. This gene encodes a preproprotein that is proteolytically processed to generate a mature azurophil granule antibiotic protein, with monocyte chemotactic and antimicrobial activity. It is also an important multifunctional inflammatory mediator. This encoded protein is a member of the serine protease gene family but it is not a serine proteinase, because the active site serine and histidine residues are replaced. The genes encoding this protein, neutrophil elastase 2, and proteinase 3 are in a cluster located at chromosome 19pter. All 3 genes are expressed coordinately and their protein products are packaged together into azurophil granules during neutrophil differentiation. [provided by RefSeq, Nov 2015]

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ACMG classification

Classification made for transcript

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=0.18635514).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
AZU1NM_001700.5 linkc.434C>A p.Ala145Asp missense_variant Exon 4 of 5 ENST00000233997.4 NP_001691.1 P20160

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
AZU1ENST00000233997.4 linkc.434C>A p.Ala145Asp missense_variant Exon 4 of 5 1 NM_001700.5 ENSP00000233997.1 P20160
AZU1ENST00000592205.5 linkc.248C>A p.Ala83Asp missense_variant Exon 4 of 4 2 ENSP00000481172.1 A0A087WXP0

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 28, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.434C>A (p.A145D) alteration is located in exon 4 (coding exon 4) of the AZU1 gene. This alteration results from a C to A substitution at nucleotide position 434, causing the alanine (A) at amino acid position 145 to be replaced by an aspartic acid (D). 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
0.19
BayesDel_addAF
Benign
-0.011
T
BayesDel_noAF
Benign
-0.25
CADD
Benign
6.1
DANN
Benign
0.27
DEOGEN2
Benign
0.32
.;T
Eigen
Benign
-0.79
Eigen_PC
Benign
-0.88
FATHMM_MKL
Benign
0.11
N
M_CAP
Benign
0.081
D
MetaRNN
Benign
0.19
T;T
MetaSVM
Benign
-0.50
T
MutationAssessor
Benign
0.94
.;L
PrimateAI
Uncertain
0.50
T
PROVEAN
Benign
-1.5
.;N
REVEL
Benign
0.22
Sift
Benign
0.62
.;T
Sift4G
Benign
0.93
T;T
Polyphen
0.17
.;B
Vest4
0.16
MutPred
0.53
.;Loss of MoRF binding (P = 0.0746);
MVP
0.86
MPC
0.45
ClinPred
0.031
T
GERP RS
1.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.19
gMVP
0.89

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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: chr19-830781; API