chr19-844020-G-A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002777.4(PRTN3):​c.355G>A​(p.Val119Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.426 in 1,603,122 control chromosomes in the GnomAD database, including 147,291 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.45 (15889 hom., cov: 30)
  • Exomes 𝑓: 0.42 (131402 hom.)
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.1993951E-5).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.52 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002777.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRTN3	NM_002777.4	MANE Select	c.355G>A	p.Val119Ile	missense	Exon 3 of 5	NP_002768.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRTN3	ENST00000234347.10	TSL:1 MANE Select	c.355G>A	p.Val119Ile	missense	Exon 3 of 5	ENSP00000234347.3
	PRTN3	ENST00000544537.2	TSL:1	c.232G>A	p.Val78Ile	missense	Exon 2 of 4	ENSP00000475174.1

Frequencies

GnomAD3 genomes AF: 0.455 AC: 68841 AN: 151464 Hom.: 15872 Cov.: 30

Gnomad AFR AF: 0.519

Gnomad AMI AF: 0.446

Gnomad AMR AF: 0.530

Gnomad ASJ AF: 0.465

Gnomad EAS AF: 0.349

Gnomad SAS AF: 0.421

Gnomad FIN AF: 0.385

Gnomad MID AF: 0.382

Gnomad NFE AF: 0.419

Gnomad OTH AF: 0.453

GnomAD2 exomes AF: 0.454 AC: 105685 AN: 232802 AF XY: 0.449

Gnomad AFR exome AF: 0.534

Gnomad AMR exome AF: 0.597

Gnomad ASJ exome AF: 0.459

Gnomad EAS exome AF: 0.359

Gnomad FIN exome AF: 0.397

Gnomad NFE exome AF: 0.426

Gnomad OTH exome AF: 0.442

GnomAD4 exome AF: 0.423 AC: 614145 AN: 1451540 Hom.: 131402 Cov.: 59 AF XY: 0.424 AC XY: 305369 AN XY: 720930

African (AFR) AF: 0.517 AC: 17226 AN: 33308

American (AMR) AF: 0.586 AC: 25472 AN: 43438

Ashkenazi Jewish (ASJ) AF: 0.455 AC: 11722 AN: 25766

East Asian (EAS) AF: 0.344 AC: 13520 AN: 39276

South Asian (SAS) AF: 0.443 AC: 37350 AN: 84276

European-Finnish (FIN) AF: 0.384 AC: 20102 AN: 52402

Middle Eastern (MID) AF: 0.428 AC: 2457 AN: 5734

European-Non Finnish (NFE) AF: 0.416 AC: 460524 AN: 1107346

Other (OTH) AF: 0.430 AC: 25772 AN: 59994

GnomAD4 genome AF: 0.455 AC: 68908 AN: 151582 Hom.: 15889 Cov.: 30 AF XY: 0.454 AC XY: 33665 AN XY: 74074

African (AFR) AF: 0.519 AC: 21446 AN: 41300

American (AMR) AF: 0.530 AC: 8073 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.465 AC: 1612 AN: 3466

East Asian (EAS) AF: 0.349 AC: 1787 AN: 5114

South Asian (SAS) AF: 0.423 AC: 2035 AN: 4808

European-Finnish (FIN) AF: 0.385 AC: 4061 AN: 10540

Middle Eastern (MID) AF: 0.373 AC: 109 AN: 292

European-Non Finnish (NFE) AF: 0.419 AC: 28431 AN: 67802

Other (OTH) AF: 0.450 AC: 950 AN: 2112

Alfa AF: 0.427 Hom.: 53195

Bravo AF: 0.469

TwinsUK AF: 0.425 AC: 1576

ALSPAC AF: 0.425 AC: 1639

ESP6500AA AF: 0.527 AC: 2319

ESP6500EA AF: 0.411 AC: 3531

ExAC AF: 0.436 AC: 52584

Asia WGS AF: 0.385 AC: 1343 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.77	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.085
DANN	Benign	0.89
DEOGEN2	Benign	0.21	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.42	T
MetaRNN	Benign	0.000012	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-1.1	N
PhyloP100		-1.7
PrimateAI	Benign	0.37	T
PROVEAN	Benign	0.31	N
REVEL	Benign	0.014
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.28	B
Vest4		0.052
MPC		0.19
ClinPred		0.0030	T
GERP RS		-3.6
Varity_R		0.034
gMVP		0.33
Mutation Taster		=90/10	polymorphism (auto)

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

Other links and lift over

dbSNP: rs351111; hg19: chr19-844020; COSMIC: COSV52255754;