rs576564400
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001379610.1(SPINK1):c.206C>T(p.Thr69Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,614,018 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001379610.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SPINK1 | NM_001379610.1 | c.206C>T | p.Thr69Ile | missense_variant | 4/4 | ENST00000296695.10 | NP_001366539.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SPINK1 | ENST00000296695.10 | c.206C>T | p.Thr69Ile | missense_variant | 4/4 | 1 | NM_001379610.1 | ENSP00000296695.5 | ||
SPINK1 | ENST00000505722.1 | n.121C>T | non_coding_transcript_exon_variant | 2/2 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152146Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 250498Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 135424
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461754Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727182
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152264Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74440
ClinVar
Submissions by phenotype
Hereditary pancreatitis Pathogenic:1Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 04, 2021 | This variant is present in population databases (rs576564400, ExAC 0.02%). This sequence change replaces threonine with isoleucine at codon 69 of the SPINK1 protein (p.Thr69Ile). The threonine residue is weakly conserved and there is a moderate physicochemical difference between threonine and isoleucine. 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 abolishes SPINK1 protein expression in an overexpression system (PMID: 22343981). This variant has been observed in an individual affected with alcoholic pancreatitis (PMID: 18182741) and in individuals with idiopathic chronic pancreatitis (PMID: 30420730). ClinVar contains an entry for this variant (Variation ID: 440299). - |
Pathogenic, criteria provided, single submitter | clinical testing | Center for Human Genetics, Inc, Center for Human Genetics, Inc | Nov 01, 2016 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 26, 2024 | 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 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Mar 27, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at