8-10525688-G-A

Variant summary

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

The NM_198464.4(PRSS55):c.103G>A(p.Ala35Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000682 in 1,613,740 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

PRSS55
NM_198464.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.00800

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 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=0.08139691).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRSS55	NM_198464.4 linkuse as main transcript	c.103G>A	p.Ala35Thr	missense_variant	1/5	ENST00000328655.8
PRSS51	XR_007060820.1 linkuse as main transcript	n.294+21742C>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.103G>A	p.Ala35Thr	missense_variant	1/5	1	NM_198464.4	P1	Q6UWB4-1
PRSS51	ENST00000523024.2 linkuse as main transcript	c.-111+21742C>T		intron_variant, NMD_transcript_variant		1
PRSS55	ENST00000522210.1 linkuse as main transcript	c.103G>A	p.Ala35Thr	missense_variant	1/5	2			Q6UWB4-2
PRSS51	ENST00000637190.1 linkuse as main transcript	c.-89+21742C>T		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000800

AC:

AN:

250124

Hom.:

AF XY:

0.00000739

AC XY:

AN XY:

135294

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000547

AC:

AN:

1461532

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727086

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000630

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152208

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

Jan 31, 2022

The c.103G>A (p.A35T) alteration is located in exon 1 (coding exon 1) of the PRSS55 gene. This alteration results from a G to A substitution at nucleotide position 103, causing the alanine (A) at amino acid position 35 to be replaced by a threonine (T). 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

0.095

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.39

Cadd

Benign

3.1

Dann

Benign

0.89

DEOGEN2

Benign

0.0011

T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.032

LIST_S2

Benign

0.53

T;T

M_CAP

Benign

0.029

MetaRNN

Benign

0.081

T;T

MetaSVM

Benign

-0.78

MutationAssessor

Benign

0.81

L;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.27

PROVEAN

Benign

0.13

N;N

REVEL

Benign

0.11

Sift

Benign

0.30

T;T

Sift4G

Benign

0.15

T;D

Polyphen

0.096

B;.

Vest4

0.15

MutPred

0.23

Gain of glycosylation at A35 (P = 0.0066);Gain of glycosylation at A35 (P = 0.0066);

MVP

0.42

MPC

0.0015

ClinPred

0.042

GERP RS

0.44

Varity_R

0.026

gMVP

0.41

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