Variant 16-31132853-G-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_002773.5(PRSS8):c.367C>A(p.His123Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000231 in 1,613,890 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00024 ( 1 hom. )

Consequence

PRSS8
NM_002773.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.75

Variant links:

Genes affected

PRSS8 (HGNC:9491): (serine protease 8) This gene encodes a member of the peptidase S1 or chymotrypsin family of serine proteases. The encoded preproprotein is proteolytically processed to generate light and heavy chains that associate via a disulfide bond to form the heterodimeric enzyme. This enzyme is highly expressed in prostate epithelia and is one of several proteolytic enzymes found in seminal fluid. This protease exhibits trypsin-like substrate specificity, cleaving protein substrates at the carboxyl terminus of lysine or arginine residues. The encoded protease partially mediates proteolytic activation of the epithelial sodium channel, a regulator of sodium balance, and may also play a role in epithelial barrier formation. [provided by RefSeq, Feb 2016]

PRSS8 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRSS8	NM_002773.5 linkuse as main transcript	c.367C>A	p.His123Asn	missense_variant	4/6	ENST00000317508.11	NP_002764.1	Q16651-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PRSS8	ENST00000317508.11 linkuse as main transcript	c.367C>A	p.His123Asn	missense_variant	4/6	1	NM_002773.5	ENSP00000319730.6	Q16651-1
PRSS8	ENST00000568261.5 linkuse as main transcript	c.205C>A	p.His69Asn	missense_variant	4/6	2		ENSP00000457750.1	Q16651-2
PRSS8	ENST00000567531.5 linkuse as main transcript	c.267-8C>A		splice_region_variant, intron_variant		3		ENSP00000457673.1	H3BUJ8
PRSS8	ENST00000567797.1 linkuse as main transcript	c.*26C>A		downstream_gene_variant		4		ENSP00000458056.1	H3BVC8

Frequencies

GnomAD3 genomes

AF:

0.000164

AC:

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000225

AC:

AN:

249248

Hom.:

AF XY:

0.000288

AC XY:

AN XY:

135202

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000869

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000359

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000372

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000238

AC:

348

AN:

1461656

Hom.:

Cov.:

AF XY:

0.000241

AC XY:

175

AN XY:

727116

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000278

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000282

Gnomad4 OTH exome

AF:

0.000133

GnomAD4 genome

AF:

0.000164

AC:

AN:

152234

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000393

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000249

Hom.:

Bravo

AF:

0.000178

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ExAC

AF:

0.000256

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000356

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

Mar 27, 2023

The c.367C>A (p.H123N) alteration is located in exon 4 (coding exon 4) of the PRSS8 gene. This alteration results from a C to A substitution at nucleotide position 367, causing the histidine (H) at amino acid position 123 to be replaced by an asparagine (N). 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

0.30

BayesDel_addAF

Benign

-0.038

BayesDel_noAF

Uncertain

0.020

CADD

Benign

DANN

Benign

0.87

DEOGEN2

Uncertain

0.75

D;.

Eigen

Benign

0.15

Eigen_PC

Benign

-0.0087

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.49

T;T

M_CAP

Uncertain

0.25

MetaRNN

Uncertain

0.64

D;D

MetaSVM

Pathogenic

0.92

MutationAssessor

Uncertain

2.5

M;.

PrimateAI

Benign

0.40

PROVEAN

Uncertain

-2.8

D;D

REVEL

Uncertain

0.52

Sift

Benign

0.20

T;T

Sift4G

Benign

0.64

T;T

Polyphen

1.0

D;.

Vest4

0.53

MVP

0.94

MPC

0.99

ClinPred

0.16

GERP RS

3.5

Varity_R

0.40

gMVP

0.91

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