Genetic Variant NM_002769.5:c.121C>T (chr7-142750635-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP6_Very_StrongBP7

The NM_002769.5(PRSS1):c.121C>T(p.Leu41Leu) 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 0.00035 ( 0 hom., cov: 37)

Exomes 𝑓: 0.00018 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

PRSS1
NM_002769.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 2.55

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:

TRB (HGNC:12155):

TRB links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP6

Variant 7-142750635-C-T is Benign according to our data. Variant chr7-142750635-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 416607.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-142750635-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=2.55 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRSS1	NM_002769.5 link	c.121C>T	p.Leu41Leu	synonymous_variant	Exon 2 of 5	ENST00000311737.12	NP_002760.1	P07477

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRSS1	ENST00000311737.12 link	c.121C>T	p.Leu41Leu	synonymous_variant	Exon 2 of 5	1	NM_002769.5	ENSP00000308720.7		P07477

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

142160

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000142

Gnomad ASJ

AF:

0.000307

Gnomad EAS

AF:

0.000200

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000203

Gnomad MID

AF:

0.00347

Gnomad NFE

AF:

0.000483

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000182

AC:

251

AN:

1380674

Hom.:

Cov.:

AF XY:

0.000177

AC XY:

122

AN XY:

689648

show subpopulations

Gnomad4 AFR exome

AF:

0.000523

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000353

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000199

Gnomad4 OTH exome

AF:

0.000417

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000351

AC:

AN:

142262

Hom.:

Cov.:

AF XY:

0.000244

AC XY:

AN XY:

69662

show subpopulations

Gnomad4 AFR

AF:

0.000314

Gnomad4 AMR

AF:

0.000142

Gnomad4 ASJ

AF:

0.000307

Gnomad4 EAS

AF:

0.000201

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000203

Gnomad4 NFE

AF:

0.000483

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0573

Hom.:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Hereditary pancreatitis

Benign:3

Sep 23, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 19, 2020

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 28, 2015

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely 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. -

not provided

Benign:1

Feb 12, 2016

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

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.69

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