19-829668-G-T

Variant summary

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

The NM_001700.5(AZU1):​c.322G>T​(p.Asp108Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000955 in 1,613,386 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000092 ( 0 hom. )

Consequence

AZU1
NM_001700.5 missense

Scores

1
6
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.511
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]

Genome browser will be placed here

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=0.21338493).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
AZU1NM_001700.5 linkc.322G>T p.Asp108Tyr missense_variant 3/5 ENST00000233997.4 NP_001691.1 P20160

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
AZU1ENST00000233997.4 linkc.322G>T p.Asp108Tyr missense_variant 3/51 NM_001700.5 ENSP00000233997.1 P20160
AZU1ENST00000592205.5 linkc.136G>T p.Asp46Tyr missense_variant 3/42 ENSP00000481172.1 A0A087WXP0

Frequencies

GnomAD3 genomes
AF:
0.000125
AC:
19
AN:
152148
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000145
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000262
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000103
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000187
AC:
47
AN:
250916
Hom.:
0
AF XY:
0.000184
AC XY:
25
AN XY:
135752
show subpopulations
Gnomad AFR exome
AF:
0.000431
Gnomad AMR exome
AF:
0.000492
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000185
Gnomad OTH exome
AF:
0.000327
GnomAD4 exome
AF:
0.0000924
AC:
135
AN:
1461120
Hom.:
0
Cov.:
38
AF XY:
0.0000880
AC XY:
64
AN XY:
726860
show subpopulations
Gnomad4 AFR exome
AF:
0.000388
Gnomad4 AMR exome
AF:
0.000358
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000692
Gnomad4 OTH exome
AF:
0.000414
GnomAD4 genome
AF:
0.000125
AC:
19
AN:
152266
Hom.:
0
Cov.:
32
AF XY:
0.000148
AC XY:
11
AN XY:
74440
show subpopulations
Gnomad4 AFR
AF:
0.000144
Gnomad4 AMR
AF:
0.000262
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000103
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.0000935
Hom.:
0
Bravo
AF:
0.000200
ESP6500AA
AF:
0.000908
AC:
4
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.000165
AC:
20
EpiCase
AF:
0.000382
EpiControl
AF:
0.000237

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 submitterclinical testingAmbry GeneticsMay 30, 2023The c.322G>T (p.D108Y) alteration is located in exon 3 (coding exon 3) of the AZU1 gene. This alteration results from a G to T substitution at nucleotide position 322, causing the aspartic acid (D) at amino acid position 108 to be replaced by a tyrosine (Y). 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
Uncertain
0.47
BayesDel_addAF
Benign
-0.15
T
BayesDel_noAF
Benign
-0.12
CADD
Benign
16
DANN
Benign
0.97
DEOGEN2
Uncertain
0.61
.;D
Eigen
Benign
-0.59
Eigen_PC
Benign
-0.97
FATHMM_MKL
Benign
0.040
N
M_CAP
Benign
0.071
D
MetaRNN
Benign
0.21
T;T
MetaSVM
Uncertain
0.25
D
MutationAssessor
Benign
1.7
.;L
PrimateAI
Uncertain
0.53
T
PROVEAN
Pathogenic
-5.4
.;D
REVEL
Benign
0.29
Sift
Uncertain
0.0070
.;D
Sift4G
Uncertain
0.020
D;D
Polyphen
1.0
.;D
Vest4
0.47
MVP
0.89
MPC
0.79
ClinPred
0.13
T
GERP RS
-2.3
Varity_R
0.21
gMVP
0.64

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs142169722; hg19: chr19-829668; API