Variant chr16-58284658-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001305173.2(PRSS54):c.586C>G(p.Pro196Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00855 in 1,613,930 control chromosomes in the GnomAD database, including 84 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0063 ( 4 hom., cov: 31)

Exomes 𝑓: 0.0088 ( 80 hom. )

Consequence

PRSS54
NM_001305173.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.80

Variant links:

Genes affected

PRSS54 (HGNC:26336): (serine protease 54) This gene encodes a putative serine-type endopeptidase containing the peptidase S1 domain. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Feb 2015]

PRSS54 links:

PRSS54 (HGNC:):

PRSS54 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0088810325).

BP6

Variant 16-58284658-G-C is Benign according to our data. Variant chr16-58284658-G-C is described in ClinVar as [Benign]. Clinvar id is 710089.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRSS54	NM_001305173.2 linkuse as main transcript	c.586C>G	p.Pro196Ala	missense_variant	6/7	ENST00000567164.6	NP_001292102.1	Q6PEW0A0A140VKC3
PRSS54	NM_001080492.2 linkuse as main transcript	c.586C>G	p.Pro196Ala	missense_variant	6/7		NP_001073961.1	Q6PEW0A0A140VKC3
PRSS54	NM_001305174.2 linkuse as main transcript	c.289C>G	p.Pro97Ala	missense_variant	5/6		NP_001292103.1	F5H6C6
PRSS54	XM_047433779.1 linkuse as main transcript	c.52C>G	p.Pro18Ala	missense_variant	2/3		XP_047289735.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRSS54	ENST00000567164.6 linkuse as main transcript	c.586C>G	p.Pro196Ala	missense_variant	6/7	1	NM_001305173.2	ENSP00000455024.1		Q6PEW0

Frequencies

GnomAD3 genomes

AF:

0.00633

AC:

963

AN:

152020

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00408

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.00675

Gnomad ASJ

AF:

0.00979

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0127

Gnomad FIN

AF:

0.00661

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00741

Gnomad OTH

AF:

0.00814

GnomAD3 exomes

AF:

0.00741

AC:

1863

AN:

251482

Hom.:

AF XY:

0.00762

AC XY:

1035

AN XY:

135912

show subpopulations

Gnomad AFR exome

AF:

0.00449

Gnomad AMR exome

AF:

0.00564

Gnomad ASJ exome

AF:

0.0102

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0115

Gnomad FIN exome

AF:

0.00707

Gnomad NFE exome

AF:

0.00817

Gnomad OTH exome

AF:

0.00912

GnomAD4 exome

AF:

0.00878

AC:

12831

AN:

1461792

Hom.:

Cov.:

AF XY:

0.00875

AC XY:

6362

AN XY:

727198

show subpopulations

Gnomad4 AFR exome

AF:

0.00505

Gnomad4 AMR exome

AF:

0.00548

Gnomad4 ASJ exome

AF:

0.0101

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0103

Gnomad4 FIN exome

AF:

0.00747

Gnomad4 NFE exome

AF:

0.00922

Gnomad4 OTH exome

AF:

0.00969

GnomAD4 genome

AF:

0.00633

AC:

963

AN:

152138

Hom.:

Cov.:

AF XY:

0.00639

AC XY:

475

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.00405

Gnomad4 AMR

AF:

0.00674

Gnomad4 ASJ

AF:

0.00979

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0127

Gnomad4 FIN

AF:

0.00661

Gnomad4 NFE

AF:

0.00743

Gnomad4 OTH

AF:

0.00806

Alfa

AF:

0.00700

Hom.:

Bravo

AF:

0.00625

TwinsUK

AF:

0.00836

AC:

ALSPAC

AF:

0.0109

AC:

ESP6500AA

AF:

0.00455

AC:

ESP6500EA

AF:

0.00907

AC:

ExAC

AF:

0.00785

AC:

953

Asia WGS

AF:

0.0170

AC:

AN:

3478

EpiCase

AF:

0.00632

EpiControl

AF:

0.00812

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 30, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.14

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.13

T;T;.;.

Eigen

Benign

0.082

Eigen_PC

Benign

0.037

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.56

.;T;T;T

MetaRNN

Benign

0.0089

T;T;T;T

MetaSVM

Uncertain

-0.049

MutationAssessor

Benign

1.8

L;L;.;.

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.6

N;N;N;N

REVEL

Uncertain

0.34

Sift

Benign

0.14

T;T;D;T

Sift4G

Uncertain

0.060

T;T;T;.

Polyphen

0.93

P;P;.;.

Vest4

0.39

MVP

0.87

MPC

0.60

ClinPred

0.027

GERP RS

3.5

Varity_R

0.18

gMVP

0.47

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over