19-829626-C-A

Variant names:

• chr19-829626-C-A
• rs374411584
• NM_001700.5:c.280C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001700.5(AZU1):​c.280C>A​(p.Arg94Ser) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R94C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: AZU1 NM_001700.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.237
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2688944).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001700.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AZU1	NM_001700.5	MANE Select	c.280C>A	p.Arg94Ser	missense	Exon 3 of 5	NP_001691.1	P20160

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AZU1	ENST00000233997.4	TSL:1 MANE Select	c.280C>A	p.Arg94Ser	missense	Exon 3 of 5	ENSP00000233997.1	P20160
	AZU1	ENST00000592205.5	TSL:2	c.94C>A	p.Arg32Ser	missense	Exon 3 of 4	ENSP00000481172.1	A0A087WXP0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.67
BayesDel_addAF	Benign	0.00044	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.41	T
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.029	N
M_CAP	Benign	0.056	D
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.36	T
MutationAssessor	Benign	0.48	N
PhyloP100		-0.24
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-2.6	D
REVEL	Uncertain	0.35
Sift	Uncertain	0.0070	D
Sift4G	Benign	0.084	T
Polyphen		1.0	D
Vest4		0.28
MutPred		0.47		Loss of MoRF binding (P = 0.0161)
MVP		0.85
MPC		0.78
ClinPred		0.88	D
GERP RS		-1.9
Varity_R		0.52
gMVP		0.59
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs374411584; hg19: chr19-829626;