chr7-142752462-T-C

Position:

• chr7-142752462-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The NM_002769.5(PRSS1):​c.486T>C​(p.Asp162=) 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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: -3.83

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]

ACMG classification

Verdict is Benign. Variant got -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 [Likely_benign]. Clinvar id is 239391.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-142752462-T-C is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-3.83 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRSS1	NM_002769.5	c.486T>C	p.Asp162=	synonymous_variant	4/5	ENST00000311737.12	NP_002760.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRSS1	ENST00000311737.12	c.486T>C	p.Asp162=	synonymous_variant	4/5	1	NM_002769.5	ENSP00000308720	P1
PRSS1	ENST00000486171.5	c.528T>C	p.Asp176=	synonymous_variant	5/6	5		ENSP00000417854
PRSS1	ENST00000492062.1	c.336T>C	p.Asp112=	synonymous_variant	3/4	2		ENSP00000419912
PRSS1	ENST00000463701.1	n.950T>C		non_coding_transcript_exon_variant	2/3	2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 63245 AN: 148028 Hom.: 1829 Cov.: 36 FAILED QC

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

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.405 AC: 585672 AN: 1447336 Hom.: 15706 Cov.: 69 AF XY: 0.400 AC XY: 288125 AN XY: 720822

Gnomad4 AFR exome AF: 0.452

Gnomad4 AMR exome AF: 0.413

Gnomad4 ASJ exome AF: 0.410

Gnomad4 EAS exome AF: 0.217

Gnomad4 SAS exome AF: 0.263

Gnomad4 FIN exome AF: 0.426

Gnomad4 NFE exome AF: 0.421

Gnomad4 OTH exome AF: 0.388

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.427 AC: 63305 AN: 148142 Hom.: 1831 Cov.: 36 AF XY: 0.424 AC XY: 30713 AN XY: 72506

Gnomad4 AFR AF: 0.517

Gnomad4 AMR AF: 0.422

Gnomad4 ASJ AF: 0.409

Gnomad4 EAS AF: 0.198

Gnomad4 SAS AF: 0.259

Gnomad4 FIN AF: 0.421

Gnomad4 NFE AF: 0.410

Gnomad4 OTH AF: 0.421

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

Submissions by phenotype

not specified Benign:5

Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 19, 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, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Apr 21, 2021	- -
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+	-	- -

Hereditary pancreatitis Benign:5

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, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	KCCC/NGS Laboratory, Kuwait Cancer Control Center	Jul 07, 2023	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Jan 14, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not provided Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.12
DANN	Benign	0.20

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

Other links and lift over

dbSNP: rs6666; hg19: chr7-142460313; COSMIC: COSV61190814; COSMIC: COSV61190814;