rs351111

Positions:

• chr19-844020-G-A
• chr19-844020-G-T

Variant summary

Our verdict is Benign. Variant got -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. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• 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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRTN3	NM_002777.4	c.355G>A	p.Val119Ile	missense_variant	3/5	ENST00000234347.10	NP_002768.3
PRTN3	XM_011528136.2	c.355G>A	p.Val119Ile	missense_variant	3/5		XP_011526438.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRTN3	ENST00000234347.10	c.355G>A	p.Val119Ile	missense_variant	3/5	1	NM_002777.4	ENSP00000234347	P1
PRTN3	ENST00000544537.2	c.232G>A	p.Val78Ile	missense_variant	2/4	1		ENSP00000475174

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

GnomAD3 exomes AF: 0.454 AC: 105685 AN: 232802 Hom.: 24281 AF XY: 0.449 AC XY: 56422 AN XY: 125706

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 SAS exome AF: 0.447

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

Gnomad4 AFR exome AF: 0.517

Gnomad4 AMR exome AF: 0.586

Gnomad4 ASJ exome AF: 0.455

Gnomad4 EAS exome AF: 0.344

Gnomad4 SAS exome AF: 0.443

Gnomad4 FIN exome AF: 0.384

Gnomad4 NFE exome AF: 0.416

Gnomad4 OTH exome AF: 0.430

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

Gnomad4 AFR AF: 0.519

Gnomad4 AMR AF: 0.530

Gnomad4 ASJ AF: 0.465

Gnomad4 EAS AF: 0.349

Gnomad4 SAS AF: 0.423

Gnomad4 FIN AF: 0.385

Gnomad4 NFE AF: 0.419

Gnomad4 OTH AF: 0.450

Alfa AF: 0.426 Hom.: 26361

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 v4.3

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;T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.42	T;T
MetaRNN	Benign	0.000012	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-1.1	N;.
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.37	T
PROVEAN	Benign	0.31	N;.
REVEL	Benign	0.014
Sift	Benign	1.0	T;.
Sift4G	Benign	1.0	T;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

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

Publications

LitVar

Other links and lift over

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