chr7-142751963-C-T
Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_002769.5(PRSS1):c.390C>T(p.Thr130=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000187 in 1,612,098 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 (★★). Synonymous variant affecting the same amino acid position (i.e. T130T) has been classified as Likely benign.
Frequency
Consequence
NM_002769.5 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -17 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRSS1 | NM_002769.5 | c.390C>T | p.Thr130= | synonymous_variant | 3/5 | ENST00000311737.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRSS1 | ENST00000311737.12 | c.390C>T | p.Thr130= | synonymous_variant | 3/5 | 1 | NM_002769.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000127 AC: 19AN: 150118Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.000104 AC: 26AN: 249854Hom.: 0 AF XY: 0.0000961 AC XY: 13AN XY: 135264
GnomAD4 exome AF: 0.000194 AC: 283AN: 1461864Hom.: 0 Cov.: 61 AF XY: 0.000179 AC XY: 130AN XY: 727234
GnomAD4 genome ? AF: 0.000126 AC: 19AN: 150234Hom.: 0 Cov.: 31 AF XY: 0.0000953 AC XY: 7AN XY: 73478
ClinVar
Submissions by phenotype
Hereditary pancreatitis Uncertain:1Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 18, 2023 | - - |
Uncertain significance, no assertion criteria provided | literature only | Forschungslabor Klinik Innere Medizin A University Medicine Greifswald | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 21, 2018 | 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
Likely benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Jun 26, 2019 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Apr 25, 2017 | Variant summary: The PRSS1 c.390C>T (p.Thr130Thr) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool (mutation taster) predicts a benign outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant may affect multiple ESE sites. However, these predictions have yet to be confirmed by functional studies. This variant was found in 28/120840 control chromosomes from ExAC at a frequency of 0.0002317, which is approximately 46 times the estimated maximal expected allele frequency of a pathogenic PRSS1 variant (0.000005), strongly supporting that this variant is likely a benign polymorphism. In addition, co-occurrence of this variant and a pathogenic PRSS1 variant (c.365_366delGCinsAT/p.Arg122His) was observed in one patient with chronic pancreatitis (Rygiel_2015). An internal sample with this variant also carries a pathogenic variant (5T_TG12) in CFTR gene. Taken together, this variant is classified as benign. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at