rs587781619
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_000455.5(STK11):c.465-3C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000125 in 1,599,262 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_000455.5 splice_region, splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
STK11 | NM_000455.5 | c.465-3C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000326873.12 | |||
STK11 | NM_001407255.1 | c.465-3C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ||||
STK11 | NR_176325.1 | n.1732-3C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
STK11 | ENST00000326873.12 | c.465-3C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_000455.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152238Hom.: 0 Cov.: 33
GnomAD4 exome AF: 6.91e-7 AC: 1AN: 1447024Hom.: 0 Cov.: 32 AF XY: 0.00000139 AC XY: 1AN XY: 718464
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152238Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74366
ClinVar
Submissions by phenotype
Peutz-Jeghers syndrome Uncertain:4
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 12, 2023 | 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. 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 is not likely to affect RNA splicing. ClinVar contains an entry for this variant (Variation ID: 141268). This variant has not been reported in the literature in individuals affected with STK11-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change falls in intron 3 of the STK11 gene. It does not directly change the encoded amino acid sequence of the STK11 protein. It affects a nucleotide within the consensus splice site. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 15, 2021 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein | Aug 02, 2022 | ACMG classification criteria: PM2 moderated - |
Uncertain significance, criteria provided, single submitter | clinical testing | Mendelics | Jul 02, 2018 | - - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 16, 2020 | The c.465-3C>T intronic variant results from a C to T substitution 3 nucleotides upstream from coding exon 4 in the STK11 gene. This nucleotide position is well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will not have any significant effect on splicing. 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