chr7-142749524-CGTGA-C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The ENST00000311737.12(PRSS1):c.40+1_40+4delGTGA variant causes a splice donor, splice region, intron change. The variant allele was found at a frequency of 0.0000206 in 145,690 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
ENST00000311737.12 splice_donor, splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PRSS1 | ENST00000311737.12 | c.40+1_40+4delGTGA | splice_donor_variant, splice_region_variant, intron_variant | Intron 1 of 4 | 1 | NM_002769.5 | ENSP00000308720.7 | |||
PRSS1 | ENST00000486171.5 | c.40+1_40+4delGTGA | splice_donor_variant, splice_region_variant, intron_variant | Intron 1 of 5 | 5 | ENSP00000417854.1 | ||||
PRSS1 | ENST00000485223.1 | n.53+1_53+4delGTGA | splice_donor_variant, splice_region_variant, intron_variant | Intron 1 of 1 | 2 | |||||
PRSS1 | ENST00000497041.1 | n.44+1_44+4delGTGA | splice_donor_variant, splice_region_variant, intron_variant | Intron 1 of 1 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000206 AC: 3AN: 145690Hom.: 0 Cov.: 34
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000282 AC: 4AN: 1418462Hom.: 0 AF XY: 0.00000142 AC XY: 1AN XY: 706042
GnomAD4 genome AF: 0.0000206 AC: 3AN: 145690Hom.: 0 Cov.: 34 AF XY: 0.0000423 AC XY: 3AN XY: 70998
ClinVar
Submissions by phenotype
Hereditary pancreatitis Uncertain:2
This sequence change falls in intron 1 of the PRSS1 gene. It does not directly change the encoded amino acid sequence of the PRSS1 protein. It affects a nucleotide within the consensus splice site. 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. This variant has not been reported in the literature in individuals affected with PRSS1-related conditions. ClinVar contains an entry for this variant (Variation ID: 528770). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. -
The c.40+3_40+6delGAGT intronic variant, located in intron 1 of the PRSS1 gene, results from a deletion of 4 nucleotides within intron 1 of the PRSS1 gene. This nucleotide region is well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice donor site. However, loss of function of PRSS1 has not been established as a mechanism of disease. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at