Variant 8-10531314-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_198464.4(PRSS55):c.367G>A(p.Val123Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00132 in 1,614,096 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0010 ( 1 hom., cov: 34)

Exomes 𝑓: 0.0014 ( 3 hom. )

Consequence

PRSS55
NM_198464.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.58

Variant links:

Genes affected

PRSS55 (HGNC:30824): (serine protease 55) This gene encodes a member of a group of membrane-anchored chymotrypsin (S1)-like serine proteases. The enocoded protein is primarily expressed in the Leydig and Sertoli cells of the testis and may be involved in male fertility. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2010]

PRSS55 links:

PRSS51 (HGNC:37321): (serine protease 51) Predicted to enable serine-type endopeptidase activity. Predicted to be involved in proteolysis. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

PRSS51 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.020493835).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRSS55	NM_198464.4 linkuse as main transcript	c.367G>A	p.Val123Met	missense_variant	3/5	ENST00000328655.8
PRSS51	XR_007060820.1 linkuse as main transcript	n.294+16116C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRSS55	ENST00000328655.8 linkuse as main transcript	c.367G>A	p.Val123Met	missense_variant	3/5	1	NM_198464.4	P1	Q6UWB4-1

Frequencies

GnomAD3 genomes

AF:

0.00101

AC:

153

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00124

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00169

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000960

AC:

240

AN:

249870

Hom.:

AF XY:

0.000887

AC XY:

120

AN XY:

135300

show subpopulations

Gnomad AFR exome

AF:

0.000371

Gnomad AMR exome

AF:

0.00124

Gnomad ASJ exome

AF:

0.000897

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000261

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00146

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.00135

AC:

1974

AN:

1461788

Hom.:

Cov.:

AF XY:

0.00133

AC XY:

968

AN XY:

727192

show subpopulations

Gnomad4 AFR exome

AF:

0.000478

Gnomad4 AMR exome

AF:

0.00134

Gnomad4 ASJ exome

AF:

0.000880

Gnomad4 EAS exome

AF:

0.000252

Gnomad4 SAS exome

AF:

0.000417

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.00156

Gnomad4 OTH exome

AF:

0.00118

GnomAD4 genome

AF:

0.00100

AC:

153

AN:

152308

Hom.:

Cov.:

AF XY:

0.000859

AC XY:

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.00124

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00169

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00134

Hom.:

Bravo

AF:

0.00133

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00186

AC:

ExAC

AF:

0.000988

AC:

120

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00224

EpiControl

AF:

0.00154

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 25, 2023

The c.367G>A (p.V123M) alteration is located in exon 3 (coding exon 3) of the PRSS55 gene. This alteration results from a G to A substitution at nucleotide position 367, causing the valine (V) at amino acid position 123 to be replaced by a methionine (M). 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

0.17

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.22

Cadd

Benign

Dann

Benign

0.94

DEOGEN2

Benign

0.22

T;.

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.64

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.67

T;T

M_CAP

Benign

0.065

MetaRNN

Benign

0.020

T;T

MetaSVM

Uncertain

-0.28

MutationAssessor

Benign

1.6

L;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.43

PROVEAN

Benign

-1.2

N;N

REVEL

Uncertain

0.36

Sift

Benign

0.082

T;T

Sift4G

Benign

0.31

T;T

Polyphen

0.45

B;.

Vest4

0.30

MVP

0.44

MPC

0.0016

ClinPred

0.0079

GERP RS

2.8

Varity_R

0.065

gMVP

0.65

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

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