chr7-142749475-C-A
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_002769.5(PRSS1):c.-10C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000229 in 1,613,984 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 Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00014 ( 0 hom., cov: 34)
Exomes 𝑓: 0.000011 ( 0 hom. )
Consequence
PRSS1
NM_002769.5 5_prime_UTR
NM_002769.5 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.743
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 -8 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BS2
?
High AC in GnomAd at 21 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRSS1 | NM_002769.5 | c.-10C>A | 5_prime_UTR_variant | 1/5 | ENST00000311737.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRSS1 | ENST00000311737.12 | c.-10C>A | 5_prime_UTR_variant | 1/5 | 1 | NM_002769.5 | P1 | ||
PRSS1 | ENST00000486171.5 | c.-10C>A | 5_prime_UTR_variant | 1/6 | 5 | ||||
PRSS1 | ENST00000485223.1 | n.4C>A | non_coding_transcript_exon_variant | 1/2 | 2 | ||||
PRSS1 | ENST00000497041.1 | upstream_gene_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000138 AC: 21AN: 152160Hom.: 0 Cov.: 34
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GnomAD3 exomes AF: 0.0000358 AC: 9AN: 251480Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135910
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GnomAD4 exome AF: 0.0000109 AC: 16AN: 1461824Hom.: 0 Cov.: 47 AF XY: 0.0000138 AC XY: 10AN XY: 727212
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GnomAD4 genome ? AF: 0.000138 AC: 21AN: 152160Hom.: 0 Cov.: 34 AF XY: 0.000175 AC XY: 13AN XY: 74334
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Feb 08, 2023 | Variant summary: PRSS1 c.-10C>A is located in the untranslated mRNA region upstream of the initiation codon. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 3.6e-05 in 251480 control chromosomes, predominantly at a frequency of 0.00055 within the African or African-American subpopulation in the gnomAD database. These observations need to be cautiously considered due to the potential of PRSS1 pseudogene being captured at this site and therefore, the available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.-10C>A in individuals affected with Chronic Pancreatitis Risk and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at