7-142753014-T-C

Position:

chr7-142753014-T-C

Variant summary

Our verdict is Benign. Variant got -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

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 links:

PRSS1 (HGNC:):

PRSS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 [Likely_benign]. Clinvar id is 258803.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-142753014-T-C is described in Lovd as [Benign].

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/exons	MANE	Protein	UniProt
PRSS1	NM_002769.5 linkuse as main transcript	c.738T>C	p.Asn246Asn	synonymous_variant	5/5	ENST00000311737.12	NP_002760.1	P07477

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PRSS1	ENST00000311737.12 linkuse as main transcript	c.738T>C	p.Asn246Asn	synonymous_variant	5/5	1	NM_002769.5	ENSP00000308720.7	P07477
PRSS1	ENST00000486171.5 linkuse as main transcript	c.780T>C	p.Asn260Asn	synonymous_variant	6/6	5		ENSP00000417854.1	E7EQ64
PRSS1	ENST00000492062.1 linkuse as main transcript	c.*142T>C		3_prime_UTR_variant	4/4	2		ENSP00000419912.2	H0Y8D1
PRSS1	ENST00000463701.1 linkuse as main transcript	n.1202T>C		non_coding_transcript_exon_variant	3/3	2

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

GnomAD3 exomes

AF:

0.508

AC:

127743

AN:

251370

Hom.:

34469

AF XY:

0.502

AC XY:

68205

AN XY:

135872

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 SAS exome

AF:

0.305

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

Gnomad4 AFR exome

AF:

0.431

Gnomad4 AMR exome

AF:

0.567

Gnomad4 ASJ exome

AF:

0.562

Gnomad4 EAS exome

AF:

0.248

Gnomad4 SAS exome

AF:

0.315

Gnomad4 FIN exome

AF:

0.601

Gnomad4 NFE exome

AF:

0.576

Gnomad4 OTH exome

AF:

0.509

GnomAD4 genome

AF:

0.527

AC:

78405

AN:

148760

Hom.:

21021

Cov.:

AF XY:

0.523

AC XY:

38000

AN XY:

72726

show subpopulations

Gnomad4 AFR

AF:

0.464

Gnomad4 AMR

AF:

0.575

Gnomad4 ASJ

AF:

0.576

Gnomad4 EAS

AF:

0.225

Gnomad4 SAS

AF:

0.309

Gnomad4 FIN

AF:

0.602

Gnomad4 NFE

AF:

0.577

Gnomad4 OTH

AF:

0.532

Alfa

AF:

0.550

Hom.:

11513

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

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Oct 07, 2021	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 15, 2017	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. -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

Hereditary pancreatitis

Benign:5

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Oct 25, 2021	- -
Benign, criteria provided, single submitter	clinical testing	KCCC/NGS Laboratory, Kuwait Cancer Control Center	Jul 07, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Ambry Genetics	Nov 26, 2014	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. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Jan 14, 2021	- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

2.0

DANN

Benign

0.30

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