rs761068371

Variant names:

• chr7-142750646-C-A
• rs761068371
• NM_002769.5:c.132C>A

Your query was ambiguous. Multiple possible variants found:

• chr7-142750646-C-A
• chr7-142750646-C-G
• chr7-142750646-C-T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_002769.5(PRSS1):​c.132C>A​(p.Gly44Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. G44G) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 37)
• Consequence: PRSS1 NM_002769.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.813
• Publications: 0 publications found

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

TRB (HGNC:12155):

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 7-142750646-C-A is Benign according to our data. Variant chr7-142750646-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1770096.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.813 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002769.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRSS1	NM_002769.5	MANE Select	c.132C>A	p.Gly44Gly	synonymous	Exon 2 of 5	NP_002760.1
	PRSS1	NR_172947.1		n.145C>A		non_coding_transcript_exon	Exon 2 of 5
	PRSS1	NR_172948.1		n.145C>A		non_coding_transcript_exon	Exon 2 of 5

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRSS1	ENST00000311737.12	TSL:1 MANE Select	c.132C>A	p.Gly44Gly	synonymous	Exon 2 of 5	ENSP00000308720.7
	PRSS1	ENST00000486171.5	TSL:5	c.132C>A	p.Gly44Gly	synonymous	Exon 2 of 6	ENSP00000417854.1
	PRSS1	ENST00000492062.2	TSL:2	c.132C>A	p.Gly44Gly	synonymous	Exon 2 of 5	ENSP00000419912.2

Frequencies

GnomAD3 genomes Cov.: 37

GnomAD4 exome Cov.: 82

GnomAD4 genome Cov.: 37

Alfa AF: 0.00 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Hereditary pancreatitis Benign:1

Aug 17, 2020

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.

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	7.2
DANN	Benign	0.44
PhyloP100		-0.81
PromoterAI		-0.0036	Neutral
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs761068371; hg19: chr7-142458497; COSMIC: COSV61190236; COSMIC: COSV61190236;