rs6667

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002769.5(PRSS1):c.738T>C(p.Asn246Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.544 in 1,609,686 control chromosomes in the GnomAD database, including 244,145 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.53 ( 21021 hom., cov: 26)

Exomes 𝑓: 0.55 ( 223124 hom. )

Consequence

PRSS1
NM_002769.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.244

Publications

28 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 7-142753014-T-C is Benign according to our data. Variant chr7-142753014-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 258803.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.244 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.572 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRSS1	NM_002769.5 link	c.738T>C	p.Asn246Asn	synonymous_variant	Exon 5 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.738T>C	p.Asn246Asn	synonymous_variant	Exon 5 of 5	1	NM_002769.5	ENSP00000308720.7	P07477
PRSS1	ENST00000486171.5 link	c.780T>C	p.Asn260Asn	synonymous_variant	Exon 6 of 6	5		ENSP00000417854.1	E7EQ64
PRSS1	ENST00000463701.1 link	n.1202T>C		non_coding_transcript_exon_variant	Exon 3 of 3	2
PRSS1	ENST00000492062.2 link	c.*142T>C		3_prime_UTR_variant	Exon 5 of 5	2		ENSP00000419912.2	H0Y8D1

Frequencies

GnomAD3 genomes

AF:

0.527

AC:

78354

AN:

148648

Hom.:

21011

Cov.:

show subpopulations

Gnomad AFR

AF:

0.464

Gnomad AMI

AF:

0.526

Gnomad AMR

AF:

0.575

Gnomad ASJ

AF:

0.576

Gnomad EAS

AF:

0.225

Gnomad SAS

AF:

0.309

Gnomad FIN

AF:

0.602

Gnomad MID

AF:

0.430

Gnomad NFE

AF:

0.577

Gnomad OTH

AF:

0.536

GnomAD2 exomes

AF:

0.508

AC:

127743

AN:

251370

AF XY:

0.502

show subpopulations

Gnomad AFR exome

AF:

0.432

Gnomad AMR exome

AF:

0.561

Gnomad ASJ exome

AF:

0.562

Gnomad EAS exome

AF:

0.229

Gnomad FIN exome

AF:

0.606

Gnomad NFE exome

AF:

0.578

Gnomad OTH exome

AF:

0.531

GnomAD4 exome

AF:

0.546

AC:

797113

AN:

1460926

Hom.:

223124

Cov.:

AF XY:

0.539

AC XY:

391917

AN XY:

726840

show subpopulations

African (AFR)

AF:

0.431

AC:

14393

AN:

33390

American (AMR)

AF:

0.567

AC:

25344

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.562

AC:

14673

AN:

26126

East Asian (EAS)

AF:

0.248

AC:

9862

AN:

39694

South Asian (SAS)

AF:

0.315

AC:

27127

AN:

86240

European-Finnish (FIN)

AF:

0.601

AC:

32106

AN:

53416

Middle Eastern (MID)

AF:

0.437

AC:

2520

AN:

5762

European-Non Finnish (NFE)

AF:

0.576

AC:

640358

AN:

1111208

Other (OTH)

AF:

0.509

AC:

30730

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

19630

39260

58890

78520

98150

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17458

34916

52374

69832

87290

<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

AF:

0.527

AC:

78405

AN:

148760

Hom.:

21021

Cov.:

AF XY:

0.523

AC XY:

38000

AN XY:

72726

show subpopulations

African (AFR)

AF:

0.464

AC:

18031

AN:

38880

American (AMR)

AF:

0.575

AC:

8666

AN:

15072

Ashkenazi Jewish (ASJ)

AF:

0.576

AC:

1993

AN:

3460

East Asian (EAS)

AF:

0.225

AC:

1149

AN:

5102

South Asian (SAS)

AF:

0.309

AC:

1463

AN:

4732

European-Finnish (FIN)

AF:

0.602

AC:

6302

AN:

10466

Middle Eastern (MID)

AF:

0.429

AC:

126

AN:

294

European-Non Finnish (NFE)

AF:

0.577

AC:

39097

AN:

67776

Other (OTH)

AF:

0.532

AC:

1105

AN:

2078

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

1806

3611

5417

7222

9028

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

678

1356

2034

2712

3390

<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:

0.543

Hom.:

15043

Bravo

AF:

0.518

Asia WGS

AF:

0.273

AC:

955

AN:

3478

EpiCase

AF:

0.566

EpiControl

AF:

0.577

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

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

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

- -

Oct 07, 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

- -

Dec 15, 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

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

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

- -

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. -

Oct 25, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

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

-0.73

CADD

Benign

2.0

(source)

DANN

Benign

0.30

PhyloP100

0.24

Mutation Taster

=97/3

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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