Variant 1-227816170-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_183062.3(PRSS38):c.229G>A(p.Val77Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00409 in 1,613,584 control chromosomes in the GnomAD database, including 182 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 0.019 ( 94 hom., cov: 32)

Exomes 𝑓: 0.0026 ( 88 hom. )

Consequence

PRSS38
NM_183062.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.16

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 Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003953874).

BP6

Variant 1-227816170-G-A is Benign according to our data. Variant chr1-227816170-G-A is described in ClinVar as [Benign]. Clinvar id is 780307.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0613 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRSS38	NM_183062.3 linkuse as main transcript	c.229G>A	p.Val77Met	missense_variant	2/5	ENST00000366757.4	NP_898885.1	A1L453
PRSS38	NM_001374657.2 linkuse as main transcript	c.229G>A	p.Val77Met	missense_variant	2/4		NP_001361586.1
PRSS38	XM_011544175.3 linkuse as main transcript	c.229G>A	p.Val77Met	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.229G>A	p.Val77Met	missense_variant	2/5	1	NM_183062.3	ENSP00000355719.3		A1L453

Frequencies

GnomAD3 genomes

AF:

0.0187

AC:

2848

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0635

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00648

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0122

Gnomad SAS

AF:

0.00249

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000294

Gnomad OTH

AF:

0.0115

GnomAD3 exomes

AF:

0.00549

AC:

1373

AN:

250108

Hom.:

AF XY:

0.00418

AC XY:

566

AN XY:

135388

show subpopulations

Gnomad AFR exome

AF:

0.0644

Gnomad AMR exome

AF:

0.00344

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00810

Gnomad SAS exome

AF:

0.00105

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000177

Gnomad OTH exome

AF:

0.00278

GnomAD4 exome

AF:

0.00256

AC:

3745

AN:

1461310

Hom.:

Cov.:

AF XY:

0.00236

AC XY:

1719

AN XY:

727004

show subpopulations

Gnomad4 AFR exome

AF:

0.0634

Gnomad4 AMR exome

AF:

0.00369

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0226

Gnomad4 SAS exome

AF:

0.00116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000132

Gnomad4 OTH exome

AF:

0.00490

GnomAD4 genome

AF:

0.0187

AC:

2850

AN:

152274

Hom.:

Cov.:

AF XY:

0.0181

AC XY:

1349

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.0634

Gnomad4 AMR

AF:

0.00647

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0122

Gnomad4 SAS

AF:

0.00249

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000294

Gnomad4 OTH

AF:

0.0114

Alfa

AF:

0.00373

Hom.:

Bravo

AF:

0.0214

ESP6500AA

AF:

0.0576

AC:

254

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.00676

AC:

821

Asia WGS

AF:

0.0110

AC:

AN:

3478

EpiCase

AF:

0.000382

EpiControl

AF:

0.000119

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	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 18, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.027

LIST_S2

Benign

0.78

MetaRNN

Benign

0.0040

MetaSVM

Benign

-0.64

MutationAssessor

Benign

0.80

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.89

REVEL

Uncertain

0.41

Sift

Uncertain

0.012

Sift4G

Uncertain

0.015

Polyphen

1.0

Vest4

0.40

MVP

0.79

MPC

0.31

ClinPred

0.036

GERP RS

-2.1

Varity_R

0.16

gMVP

0.23

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