Variant chr1-227815735-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.19G>A(p.Val7Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00369 in 1,599,754 control chromosomes in the GnomAD database, including 190 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.020 ( 114 hom., cov: 31)

Exomes 𝑓: 0.0020 ( 76 hom. )

Consequence

PRSS38
NM_183062.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.88

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=0.0021394491).

BP6

Variant 1-227815735-G-A is Benign according to our data. Variant chr1-227815735-G-A is described in ClinVar as [Benign]. Clinvar id is 775676.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0649 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.19G>A	p.Val7Ile	missense_variant	1/5	ENST00000366757.4	NP_898885.1	A1L453
PRSS38	NM_001374657.2 linkuse as main transcript	c.19G>A	p.Val7Ile	missense_variant	1/4		NP_001361586.1
PRSS38	XM_011544175.3 linkuse as main transcript	c.19G>A	p.Val7Ile	missense_variant	1/5		XP_011542477.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRSS38	ENST00000366757.4 linkuse as main transcript	c.19G>A	p.Val7Ile	missense_variant	1/5	1	NM_183062.3	ENSP00000355719.3		A1L453

Frequencies

GnomAD3 genomes

AF:

0.0195

AC:

2968

AN:

152116

Hom.:

114

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0671

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00870

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000279

Gnomad OTH

AF:

0.0125

GnomAD3 exomes

AF:

0.00526

AC:

1283

AN:

243922

Hom.:

AF XY:

0.00377

AC XY:

501

AN XY:

132762

show subpopulations

Gnomad AFR exome

AF:

0.0696

Gnomad AMR exome

AF:

0.00367

Gnomad ASJ exome

AF:

0.00219

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000233

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000209

Gnomad OTH exome

AF:

0.00271

GnomAD4 exome

AF:

0.00202

AC:

2924

AN:

1447520

Hom.:

Cov.:

AF XY:

0.00175

AC XY:

1255

AN XY:

717898

show subpopulations

Gnomad4 AFR exome

AF:

0.0668

Gnomad4 AMR exome

AF:

0.00418

Gnomad4 ASJ exome

AF:

0.00300

Gnomad4 EAS exome

AF:

0.0000254

Gnomad4 SAS exome

AF:

0.000129

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000176

Gnomad4 OTH exome

AF:

0.00408

GnomAD4 genome

AF:

0.0195

AC:

2974

AN:

152234

Hom.:

114

Cov.:

AF XY:

0.0194

AC XY:

1447

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.0670

Gnomad4 AMR

AF:

0.00869

Gnomad4 ASJ

AF:

0.00346

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000279

Gnomad4 OTH

AF:

0.0123

Alfa

AF:

0.00547

Hom.:

Bravo

AF:

0.0223

ESP6500AA

AF:

0.0667

AC:

294

ESP6500EA

AF:

0.000582

AC:

ExAC

AF:

0.00612

AC:

743

Asia WGS

AF:

0.00375

AC:

AN:

3478

EpiCase

AF:

0.000328

EpiControl

AF:

0.000417

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	Jul 25, 2017	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.54

CADD

Benign

1.9

DANN

Benign

0.96

DEOGEN2

Benign

0.0010

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.045

LIST_S2

Benign

0.26

MetaRNN

Benign

0.0021

MetaSVM

Benign

-0.89

MutationAssessor

Benign

0.0

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-0.070

REVEL

Benign

0.047

Sift

Benign

0.071

Sift4G

Benign

0.47

Polyphen

0.035

Vest4

0.13

MVP

0.57

MPC

0.049

ClinPred

0.0038

GERP RS

0.28

Varity_R

0.033

gMVP

0.25

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