19-1219368-T-C
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PM1PM2PP3_StrongPP5_Moderate
The NM_000455.5(STK11):c.419T>C(p.Leu140Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. L140L) has been classified as Likely benign.
Frequency
Consequence
NM_000455.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
STK11 | NM_000455.5 | c.419T>C | p.Leu140Pro | missense_variant | 3/10 | ENST00000326873.12 | |
STK11 | NM_001407255.1 | c.419T>C | p.Leu140Pro | missense_variant | 3/9 | ||
STK11 | NR_176325.1 | n.1686T>C | non_coding_transcript_exon_variant | 4/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
STK11 | ENST00000326873.12 | c.419T>C | p.Leu140Pro | missense_variant | 3/10 | 1 | NM_000455.5 | P1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome Cov.: 36
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Peutz-Jeghers syndrome Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Dec 08, 2023 | This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 140 of the STK11 protein (p.Leu140Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Peutz-Jeghers syndrome (PMID: 29419869, 30334930). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 527843). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt STK11 protein function with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at