NM_002769.5:c.486T>C

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7

The NM_002769.5(PRSS1):c.486T>C(p.Asp162Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.43 ( 1831 hom., cov: 36)

Exomes 𝑓: 0.40 ( 15706 hom. )

Failed GnomAD Quality Control

Consequence

PRSS1
NM_002769.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -3.83

Publications

29 publications found

Variant links:

Genes affected

PRSS1 (HGNC:9475): (serine protease 1) This gene encodes a trypsinogen, which is a member of the trypsin family of serine proteases. This enzyme is secreted by the pancreas and cleaved to its active form in the small intestine. It is active on peptide linkages involving the carboxyl group of lysine or arginine. Mutations in this gene are associated with hereditary pancreatitis. This gene and several other trypsinogen genes are localized to the T cell receptor beta locus on chromosome 7. [provided by RefSeq, Jul 2008]

PRSS1 Gene-Disease associations (from GenCC):

hereditary chronic pancreatitis
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, ClinGen, PanelApp Australia, Illumina, Labcorp Genetics (formerly Invitae), Ambry Genetics
malignant pancreatic neoplasm
Inheritance: AD Classification: MODERATE Submitted by: Genomics England PanelApp

PRSS1 links:

TRB (HGNC:12155):

TRB links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 7-142752462-T-C is Benign according to our data. Variant chr7-142752462-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 239391.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.83 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRSS1	NM_002769.5 link	c.486T>C	p.Asp162Asp	synonymous_variant	Exon 4 of 5	ENST00000311737.12	NP_002760.1	P07477

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PRSS1	ENST00000311737.12 link	c.486T>C	p.Asp162Asp	synonymous_variant	Exon 4 of 5	1	NM_002769.5	ENSP00000308720.7	P07477
PRSS1	ENST00000486171.5 link	c.528T>C	p.Asp176Asp	synonymous_variant	Exon 5 of 6	5		ENSP00000417854.1	E7EQ64
PRSS1	ENST00000492062.2 link	c.486T>C	p.Asp162Asp	synonymous_variant	Exon 4 of 5	2		ENSP00000419912.2	H0Y8D1
PRSS1	ENST00000463701.1 link	n.950T>C		non_coding_transcript_exon_variant	Exon 2 of 3	2

Frequencies

GnomAD3 genomes

AF:

0.427

AC:

63245

AN:

148028

Hom.:

1829

Cov.:

show subpopulations

Gnomad AFR

AF:

0.517

Gnomad AMI

AF:

0.382

Gnomad AMR

AF:

0.422

Gnomad ASJ

AF:

0.409

Gnomad EAS

AF:

0.197

Gnomad SAS

AF:

0.259

Gnomad FIN

AF:

0.421

Gnomad MID

AF:

0.327

Gnomad NFE

AF:

0.410

Gnomad OTH

AF:

0.424

GnomAD2 exomes

AF:

0.385

AC:

96253

AN:

249982

AF XY:

0.380

show subpopulations

Gnomad AFR exome

AF:

0.360

Gnomad AMR exome

AF:

0.429

Gnomad ASJ exome

AF:

0.414

Gnomad EAS exome

AF:

0.208

Gnomad FIN exome

AF:

0.425

Gnomad NFE exome

AF:

0.426

Gnomad OTH exome

AF:

0.412

GnomAD4 exome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.405

AC:

585672

AN:

1447336

Hom.:

15706

Cov.:

AF XY:

0.400

AC XY:

288125

AN XY:

720822

show subpopulations

African (AFR)

AF:

0.452

AC:

13721

AN:

30362

American (AMR)

AF:

0.413

AC:

18333

AN:

44348

Ashkenazi Jewish (ASJ)

AF:

0.410

AC:

10669

AN:

26028

East Asian (EAS)

AF:

0.217

AC:

8608

AN:

39672

South Asian (SAS)

AF:

0.263

AC:

22665

AN:

86116

European-Finnish (FIN)

AF:

0.426

AC:

22684

AN:

53306

Middle Eastern (MID)

AF:

0.353

AC:

2005

AN:

5682

European-Non Finnish (NFE)

AF:

0.421

AC:

463854

AN:

1102128

Other (OTH)

AF:

0.388

AC:

23133

AN:

59694

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

21187

42375

63562

84750

105937

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17242

34484

51726

68968

86210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.427

AC:

63305

AN:

148142

Hom.:

1831

Cov.:

AF XY:

0.424

AC XY:

30713

AN XY:

72506

show subpopulations

African (AFR)

AF:

0.517

AC:

19933

AN:

38540

American (AMR)

AF:

0.422

AC:

6339

AN:

15030

Ashkenazi Jewish (ASJ)

AF:

0.409

AC:

1409

AN:

3442

East Asian (EAS)

AF:

0.198

AC:

1015

AN:

5138

South Asian (SAS)

AF:

0.259

AC:

1228

AN:

4742

European-Finnish (FIN)

AF:

0.421

AC:

4408

AN:

10458

Middle Eastern (MID)

AF:

0.331

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.410

AC:

27670

AN:

67554

Other (OTH)

AF:

0.421

AC:

862

AN:

2046

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

1612

3224

4837

6449

8061

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

722

1444

2166

2888

3610

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.378

Hom.:

366

Asia WGS

AF:

0.273

AC:

956

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Apr 21, 2021

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dec 19, 2017

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Hereditary pancreatitis

Benign:5

Nov 26, 2014

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 30, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.12

(source)

DANN

Benign

0.20

PhyloP100

-3.8

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over