Variant 19-846268-A-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_002777.4(PRTN3):c.491A>C(p.Asp164Ala) 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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Failed GnomAD Quality Control

Consequence

PRTN3
NM_002777.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -5.28

Variant links:

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]

PRTN3 links:

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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=0.07338402).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRTN3	NM_002777.4 linkuse as main transcript	c.491A>C	p.Asp164Ala	missense_variant	4/5	ENST00000234347.10	NP_002768.3
PRTN3	XM_011528136.2 linkuse as main transcript	c.491A>C	p.Asp164Ala	missense_variant	4/5		XP_011526438.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRTN3	ENST00000234347.10 linkuse as main transcript	c.491A>C	p.Asp164Ala	missense_variant	4/5	1	NM_002777.4	ENSP00000234347	P1
PRTN3	ENST00000544537.2 linkuse as main transcript	c.368A>C	p.Asp123Ala	missense_variant	3/4	1		ENSP00000475174

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

151186

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000952

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000661

AC:

AN:

151186

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

73776

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000952

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

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 submitter

clinical testing

Ambry Genetics

Jul 06, 2021

The c.491A>C (p.D164A) alteration is located in exon 4 (coding exon 4) of the PRTN3 gene. This alteration results from a A to C substitution at nucleotide position 491, causing the aspartic acid (D) at amino acid position 164 to be replaced by an alanine (A). 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

Benign

0.15

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.42

CADD

Benign

0.0040

DANN

Benign

0.18

DEOGEN2

Benign

0.16

T;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0058

LIST_S2

Benign

0.23

T;T

M_CAP

Benign

0.037

MetaRNN

Benign

0.073

T;T

MetaSVM

Benign

-0.86

MutationAssessor

Benign

0.46

N;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.11

N;.

REVEL

Benign

0.15

Sift

Benign

0.79

T;.

Sift4G

Benign

0.74

T;T

Polyphen

0.0020

B;.

Vest4

0.12

MutPred

0.42

Gain of methylation at R159 (P = 0.0829);.;

MVP

0.57

MPC

0.27

ClinPred

0.022

GERP RS

-0.30

Varity_R

0.18

gMVP

0.54

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over