rs397507441

chr7-142750576-A-ATGACAAGAT

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1 PM2 PM4

The NM_002769.5(PRSS1):c.63_71dup(p.Asp22_Ile24dup) variant causes a inframe insertion 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.

• Frequency: Genomes: not found (cov: 40)
• Consequence: PRSS1 NM_002769.5 inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0780

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 Likely_pathogenic. Variant got 6 ACMG points.

• PM1: In a hotspot region, there are 2 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 16 uncertain in NM_002769.5
• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_002769.5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRSS1	NM_002769.5	c.63_71dup	p.Asp22_Ile24dup	inframe_insertion	2/5	ENST00000311737.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRSS1	ENST00000311737.12	c.63_71dup	p.Asp22_Ile24dup	inframe_insertion	2/5	1	NM_002769.5	P1
PRSS1	ENST00000486171.5	c.63_71dup	p.Asp22_Ile24dup	inframe_insertion	2/6	5
PRSS1	ENST00000497041.1	n.67_75dup		non_coding_transcript_exon_variant	2/2	2
PRSS1	ENST00000485223.1	n.54-52_54-44dup		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes Cov.: 40

GnomAD4 exome Cov.: 98

GnomAD4 genome Cov.: 40

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs397507441; hg19: chr7-142458427;