19-1206140-C-T
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_000455.5(STK11):c.-774C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000202 in 148,224 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000014 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0012 ( 0 hom. )
Consequence
STK11
NM_000455.5 5_prime_UTR
NM_000455.5 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.43
Genes affected
STK11 (HGNC:11389): (serine/threonine kinase 11) The protein encoded by this gene is a serine/threonine kinase that regulates cell polarity and energy metabolism and functions as a tumor suppressor. Mutations in this gene have been associated with the autosomal dominant Peutz-Jeghers syndrome, as well as with skin, pancreatic, and testicular cancers. [provided by RefSeq, May 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
STK11 | NM_000455.5 | c.-774C>T | 5_prime_UTR_variant | 1/10 | ENST00000326873.12 | NP_000446.1 | ||
STK11 | NM_001407255.1 | c.-774C>T | 5_prime_UTR_variant | 1/9 | NP_001394184.1 | |||
STK11 | NR_176325.1 | n.363C>T | non_coding_transcript_exon_variant | 1/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
STK11 | ENST00000326873.12 | c.-774C>T | 5_prime_UTR_variant | 1/10 | 1 | NM_000455.5 | ENSP00000324856 | P1 | ||
STK11 | ENST00000585465.3 | c.-774C>T | 5_prime_UTR_variant | 1/10 | 5 | ENSP00000490268 | ||||
STK11 | ENST00000585748.3 | c.-82-12277C>T | intron_variant | 3 | ENSP00000477641 | |||||
STK11 | ENST00000652231.1 | upstream_gene_variant | ENSP00000498804 |
Frequencies
GnomAD3 genomes AF: 0.0000136 AC: 2AN: 147284Hom.: 0 Cov.: 31
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GnomAD4 exome AF: 0.00120 AC: 1AN: 832Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0AN XY: 380
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GnomAD4 genome AF: 0.0000136 AC: 2AN: 147392Hom.: 0 Cov.: 31 AF XY: 0.0000139 AC XY: 1AN XY: 71786
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Peutz-Jeghers syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Computational scores
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Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at