chr7-142752543-T-C
Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_002769.5(PRSS1):c.567T>C(p.Leu189=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000782 in 1,614,018 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0041 ( 0 hom., cov: 39)
Exomes 𝑓: 0.00044 ( 0 hom. )
Consequence
PRSS1
NM_002769.5 synonymous
NM_002769.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -3.73
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.7).
BP6
?
Variant 7-142752543-T-C is Benign according to our data. Variant chr7-142752543-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 416609.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-3.73 with no splicing effect.
BS2
?
High AC in GnomAd at 615 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRSS1 | NM_002769.5 | c.567T>C | p.Leu189= | synonymous_variant | 4/5 | ENST00000311737.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRSS1 | ENST00000311737.12 | c.567T>C | p.Leu189= | synonymous_variant | 4/5 | 1 | NM_002769.5 | P1 | |
PRSS1 | ENST00000486171.5 | c.609T>C | p.Leu203= | synonymous_variant | 5/6 | 5 | |||
PRSS1 | ENST00000492062.1 | c.417T>C | p.Leu139= | synonymous_variant | 3/4 | 2 | |||
PRSS1 | ENST00000463701.1 | n.1031T>C | non_coding_transcript_exon_variant | 2/3 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00404 AC: 615AN: 152068Hom.: 0 Cov.: 39
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GnomAD4 exome AF: 0.000436 AC: 638AN: 1461832Hom.: 0 Cov.: 59 AF XY: 0.000380 AC XY: 276AN XY: 727222
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Hereditary pancreatitis Benign:4
Likely benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Jul 07, 2020 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 29, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | KCCC/NGS Laboratory, Kuwait Cancer Control Center | Jul 07, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 01, 2016 | 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 specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Aug 13, 2020 | - - |
Computational scores
Source:
Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at