Variant 1-227816093-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_183062.3(PRSS38):c.152G>A(p.Cys51Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,984 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C51G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

PRSS38
NM_183062.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.51

Variant links:

Genes affected

PRSS38 (HGNC:29625): (serine protease 38) 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]

PRSS38 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRSS38	NM_183062.3 linkuse as main transcript	c.152G>A	p.Cys51Tyr	missense_variant	2/5	ENST00000366757.4	NP_898885.1	A1L453
PRSS38	NM_001374657.2 linkuse as main transcript	c.152G>A	p.Cys51Tyr	missense_variant	2/4		NP_001361586.1
PRSS38	XM_011544175.3 linkuse as main transcript	c.152G>A	p.Cys51Tyr	missense_variant	2/5		XP_011542477.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRSS38	ENST00000366757.4 linkuse as main transcript	c.152G>A	p.Cys51Tyr	missense_variant	2/5	1	NM_183062.3	ENSP00000355719.3		A1L453

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000403

AC:

AN:

248430

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134576

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:

0.00000896

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1459984

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726170

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

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

Feb 28, 2024

The c.152G>A (p.C51Y) alteration is located in exon 2 (coding exon 2) of the PRSS38 gene. This alteration results from a G to A substitution at nucleotide position 152, causing the cysteine (C) at amino acid position 51 to be replaced by a tyrosine (Y). 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

Pathogenic

0.82

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

-0.070

CADD

Uncertain

DANN

Benign

0.96

DEOGEN2

Benign

0.26

Eigen

Benign

0.13

Eigen_PC

Benign

0.0076

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.44

M_CAP

Benign

0.018

MetaRNN

Uncertain

0.64

MetaSVM

Benign

-0.40

MutationAssessor

Benign

0.97

PrimateAI

Uncertain

0.56

PROVEAN

Pathogenic

-9.2

REVEL

Uncertain

0.38

Sift

Uncertain

0.0010

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.47

MutPred

0.66

Gain of sheet (P = 0.0266);

MVP

0.79

MPC

0.46

ClinPred

1.0

GERP RS

3.1

Varity_R

0.78

gMVP

0.60

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