19-1206324-C-T
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Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2
The NM_000455.5(STK11):c.-590C>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 0.000456 in 228,046 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 0.00046 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00044 ( 0 hom. )
Consequence
STK11
NM_000455.5 5_prime_UTR
NM_000455.5 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.58
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 Benign. Variant got -9 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000463 (70/151220) while in subpopulation NFE AF= 0.000829 (56/67536). AF 95% confidence interval is 0.000656. There are 0 homozygotes in gnomad4. There are 33 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
BS2
High AC in GnomAd4 at 70 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
STK11 | NM_000455.5 | c.-590C>T | 5_prime_UTR_variant | 1/10 | ENST00000326873.12 | NP_000446.1 | ||
STK11 | NM_001407255.1 | c.-590C>T | 5_prime_UTR_variant | 1/9 | NP_001394184.1 | |||
STK11 | NR_176325.1 | n.547C>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.-590C>T | 5_prime_UTR_variant | 1/10 | 1 | NM_000455.5 | ENSP00000324856 | P1 | ||
STK11 | ENST00000585465.3 | c.-590C>T | 5_prime_UTR_variant | 1/10 | 5 | ENSP00000490268 | ||||
STK11 | ENST00000652231.1 | c.-590C>T | 5_prime_UTR_variant | 1/9 | ENSP00000498804 | |||||
STK11 | ENST00000585748.3 | c.-82-12093C>T | intron_variant | 3 | ENSP00000477641 |
Frequencies
GnomAD3 genomes AF: 0.000463 AC: 70AN: 151112Hom.: 0 Cov.: 31
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GnomAD4 exome AF: 0.000443 AC: 34AN: 76826Hom.: 0 Cov.: 0 AF XY: 0.000282 AC XY: 10AN XY: 35482
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GnomAD4 genome AF: 0.000463 AC: 70AN: 151220Hom.: 0 Cov.: 31 AF XY: 0.000447 AC XY: 33AN XY: 73894
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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 | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
Computational scores
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Name
Calibrated prediction
Score
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