rs769459903
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 6P and 1B. PM1PP3_StrongBS2_Supporting
The NM_002769.5(PRSS1):āc.107C>Gā(p.Pro36Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000205 in 1,461,664 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Synonymous variant affecting the same amino acid position (i.e. P36P) has been classified as Likely benign.
Frequency
Consequence
NM_002769.5 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRSS1 | NM_002769.5 | c.107C>G | p.Pro36Arg | missense_variant | 2/5 | ENST00000311737.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRSS1 | ENST00000311737.12 | c.107C>G | p.Pro36Arg | missense_variant | 2/5 | 1 | NM_002769.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000657 AC: 10AN: 152218Hom.: 0 Cov.: 37
GnomAD3 exomes AF: 0.000104 AC: 26AN: 251180Hom.: 0 AF XY: 0.000103 AC XY: 14AN XY: 135744
GnomAD4 exome AF: 0.0000205 AC: 30AN: 1461664Hom.: 0 Cov.: 85 AF XY: 0.0000220 AC XY: 16AN XY: 727140
GnomAD4 genome ? Data not reliable, filtered out with message: AS_VQSR AF: 0.0000656 AC: 10AN: 152336Hom.: 0 Cov.: 37 AF XY: 0.0000940 AC XY: 7AN XY: 74490
ClinVar
Submissions by phenotype
Hereditary pancreatitis Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 20, 2023 | The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies have shown that this missense change affects PRSS1 function (PMID: 23455445). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt PRSS1 protein function. ClinVar contains an entry for this variant (Variation ID: 459181). This missense change has been observed in individual(s) with pancreatitis and diabetes (PMID: 16791840, 23951356, 29555771). This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 36 of the PRSS1 protein (p.Pro36Arg). - |
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 22, 2024 | The p.P36R variant (also known as c.107C>G), located in coding exon 2 of the PRSS1 gene, results from a C to G substitution at nucleotide position 107. The proline at codon 36 is replaced by arginine, an amino acid with dissimilar properties. This alteration has been identified in individuals with idiopathic chronic pancreatitis (Masson E et al. PLoS One 2013 Aug;8(8):e73522; Chen JM et al. Eur J Hum Genet 2000 Jul;8(7):473-9) as well as in individuals with diabetes identified from a cohort of adults undergoing whole genome sequencing to determine risk for chronic illness (Perkins BA et al. Proc Natl Acad Sci U S A 2018 04;115(14):3686-3691). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Hereditary pancreatitis;C0268417:Trypsinogen deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at