rs878854607
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PM4_Supporting
The NM_001379610.1(SPINK1):c.131_132insTGA(p.Asp44_Pro44insAsp) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Consequence
SPINK1
NM_001379610.1 inframe_insertion
NM_001379610.1 inframe_insertion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.03
Genes affected
SPINK1 (HGNC:11244): (serine peptidase inhibitor Kazal type 1) The protein encoded by this gene is a trypsin inhibitor, which is secreted from pancreatic acinar cells into pancreatic juice. It is thought to function in the prevention of trypsin-catalyzed premature activation of zymogens within the pancreas and the pancreatic duct. Mutations in this gene are associated with hereditary pancreatitis and tropical calcific pancreatitis. [provided by RefSeq, Oct 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PM4
?
Nonframeshift variant in NON repetitive region in NM_001379610.1. Strenght limited to Supporting due to length of the change: 1aa.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SPINK1 | NM_001379610.1 | c.131_132insTGA | p.Asp44_Pro44insAsp | inframe_insertion | 3/4 | ENST00000296695.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SPINK1 | ENST00000296695.10 | c.131_132insTGA | p.Asp44_Pro44insAsp | inframe_insertion | 3/4 | 1 | NM_001379610.1 | P1 | |
SPINK1 | ENST00000510027.2 | c.131_132insTGA | p.Asp44_Pro44insAsp | inframe_insertion | 3/3 | 3 | |||
SPINK1 | ENST00000505722.1 | n.46_47insTGA | non_coding_transcript_exon_variant | 1/2 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 30
GnomAD4 exome
Cov.:
30
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Hereditary pancreatitis Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 18, 2018 | This variant, c.129_131dupTGA, results in the insertion of 1 amino acid to the SPINK1 protein (p.Asp44dup), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with SPINK1-related disease. ClinVar contains an entry for this variant (Variation ID: 239505). Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the duplicated amino acid is currently unknown. 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. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at