rs1555734984
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM1PM2PM5PP3
The NM_000455.5(STK11):c.157G>A(p.Asp53Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,650 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D53E) has been classified as Uncertain significance.
Frequency
Consequence
NM_000455.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
STK11 | NM_000455.5 | c.157G>A | p.Asp53Asn | missense_variant | 1/10 | ENST00000326873.12 | |
STK11 | NM_001407255.1 | c.157G>A | p.Asp53Asn | missense_variant | 1/9 | ||
STK11 | NR_176325.1 | n.1293G>A | non_coding_transcript_exon_variant | 1/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
STK11 | ENST00000326873.12 | c.157G>A | p.Asp53Asn | missense_variant | 1/10 | 1 | NM_000455.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461650Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 727098
GnomAD4 genome ? Cov.: 31
ClinVar
Submissions by phenotype
Peutz-Jeghers syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 23, 2021 | 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. 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. ClinVar contains an entry for this variant (Variation ID: 571654). 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 replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 53 of the STK11 protein (p.Asp53Asn). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at