19-844020-G-T

Variant names:

• chr19-844020-G-T
• rs351111
• NM_002777.4:c.355G>T

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_002777.4(PRTN3):​c.355G>T​(p.Val119Phe) 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 pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 30)
• Consequence: PRTN3 NM_002777.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.67
• Publications: 47 publications found

Genes affected

PRTN3 (HGNC:9495): (proteinase 3) Enables enzyme binding activity; serine-type endopeptidase activity; and signaling receptor binding activity. Involved in several processes, including mature conventional dendritic cell differentiation; membrane protein ectodomain proteolysis; and neutrophil extravasation. Located in azurophil granule lumen; cytosol; and plasma membrane raft. Colocalizes with plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.953

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRTN3	NM_002777.4	c.355G>T	p.Val119Phe	missense_variant	Exon 3 of 5	ENST00000234347.10	NP_002768.3
PRTN3	XM_011528136.2	c.355G>T	p.Val119Phe	missense_variant	Exon 3 of 5		XP_011526438.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRTN3	ENST00000234347.10	c.355G>T	p.Val119Phe	missense_variant	Exon 3 of 5	1	NM_002777.4	ENSP00000234347.3
PRTN3	ENST00000544537.2	c.232G>T	p.Val78Phe	missense_variant	Exon 2 of 4	1		ENSP00000475174.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 59

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 53195

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.59
BayesDel_addAF	Benign	-0.018	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.65	D;D
Eigen	Benign	-0.74
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.080	N
LIST_S2	Benign	0.66	T;T
M_CAP	Pathogenic	0.37	D
MetaRNN	Pathogenic	0.95	D;D
MetaSVM	Benign	-0.66	T
MutationAssessor	Benign	1.9	L;.
PhyloP100		-1.7
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-3.2	D;.
REVEL	Benign	0.25
Sift	Uncertain	0.0050	D;.
Sift4G	Uncertain	0.0040	D;D
Vest4		0.65
ClinPred		0.84	D
GERP RS		-3.6
Varity_R		0.33
gMVP		0.84
Mutation Taster		=89/11	polymorphism

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

Other links and lift over

dbSNP: rs351111; hg19: chr19-844020;