7-142751877-A-T

Variant names:

• chr7-142751877-A-T
• rs754618801
• NM_002769.5:c.304A>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_002769.5(PRSS1):​c.304A>T​(p.Lys102*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 31)
• Consequence: PRSS1 NM_002769.5 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.11
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.304A>T	p.Lys102*	stop_gained	Exon 3 of 5	NP_002760.1
	PRSS1	NR_172947.1		n.246A>T		non_coding_transcript_exon	Exon 3 of 5
	PRSS1	NR_172948.1		n.243A>T		non_coding_transcript_exon	Exon 3 of 5

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRSS1	ENST00000311737.12	TSL:1 MANE Select	c.304A>T	p.Lys102*	stop_gained	Exon 3 of 5	ENSP00000308720.7
	PRSS1	ENST00000486171.5	TSL:5	c.346A>T	p.Lys116*	stop_gained	Exon 4 of 6	ENSP00000417854.1
	PRSS1	ENST00000492062.2	TSL:2	c.304A>T	p.Lys102*	stop_gained	Exon 3 of 5	ENSP00000419912.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 72

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.095	D
BayesDel_noAF	Benign	-0.10
CADD	Uncertain	25
DANN	Benign	0.93
Eigen	Benign	-0.68
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0081	N
PhyloP100		-4.1
Vest4		0.74
GERP RS		-5.2
Mutation Taster		=19/181	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.41		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.25		Position offset: 49
DS_DG_spliceai		0.41		Position offset: -2

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

Other links and lift over

dbSNP: rs754618801; hg19: chr7-142459728;