rs587782259
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_000455.5(STK11):c.*8C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000277 in 1,513,214 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000455.5 3_prime_UTR
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
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STK11 | NM_000455.5 | c.*8C>T | 3_prime_UTR_variant | Exon 9 of 10 | ENST00000326873.12 | NP_000446.1 | ||
STK11 | NR_176325.1 | n.2577C>T | non_coding_transcript_exon_variant | Exon 10 of 11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
STK11 | ENST00000326873.12 | c.*8C>T | 3_prime_UTR_variant | Exon 9 of 10 | 1 | NM_000455.5 | ENSP00000324856.6 | |||
STK11 | ENST00000585748.3 | c.*8C>T | 3_prime_UTR_variant | Exon 11 of 12 | 3 | ENSP00000477641.2 |
Frequencies
GnomAD3 genomes AF: 0.000256 AC: 39AN: 152240Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000304 AC: 34AN: 112010Hom.: 0 AF XY: 0.000258 AC XY: 16AN XY: 62086
GnomAD4 exome AF: 0.000279 AC: 380AN: 1360974Hom.: 0 Cov.: 31 AF XY: 0.000276 AC XY: 185AN XY: 669254
GnomAD4 genome AF: 0.000256 AC: 39AN: 152240Hom.: 0 Cov.: 33 AF XY: 0.000215 AC XY: 16AN XY: 74362
ClinVar
Submissions by phenotype
not provided Benign:6
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STK11: BP4, BP7 -
not specified Uncertain:2Benign:2
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This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
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Hereditary cancer-predisposing syndrome Uncertain:1Benign:2
The c.*8C>T variant is located in the 3' untranslated region (3 UTR) of the STK11 gene. This variant results from a C to T substitution the last translated codon. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 4744 samples (9488 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.01% (greater than 46000 alleles tested) in our clinical cohort. This nucleotide position is not well conserved in available vertebrate species, and thymine is the reference nucleotide in several species. Since supporting evidence is limited at this time, the clinical significance of c.*8C>T remains unclear. -
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Peutz-Jeghers syndrome Benign:3
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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 allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -
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Breast and/or ovarian cancer Uncertain:1
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Malignant tumor of breast Benign:1
The STK11 c.*8C>T variant was not identified in the literature nor was it identified in the Cosmic, MutDB, LOVD 3.0, Zhejiang Colon Cancer Database, Insight Hereditary Tumors Database, databases. The variant was identified in dbSBP (ID: rs587782259) “With Uncertain significance” allele, ClinVar (classified with conflicting interpretations of pathogenicity; classified benign by GeneDx, likely benign by Illumina and uncertain significance by Ambry Genetics), Clinvitae (3x), and in control databases in 42 of 138760 chromosomes at a frequency of 0.0003 increasing the likelihood that this may be a low frequency benign variant in certain populations of origin (Genome Aggregation Consortium Feb 27, 2017), identified in the following populations: African in 1 of 13784 chromosomes (frequency: 0.00007), Other in 2 of 3874 chromosomes (frequency: 0.0005), Latino in 11 of 18642 chromosomes (frequency: 0.0006), European (Non-Finnish) in 26 of 55232 chromosomes (frequency: 0.0005), and Ashkenazi Jewish in 2 of 6458 chromosomes (frequency: 0.0003). The variant occurs 8 nucleotides downstream of the final codon, outside of the splicing consensus sequence, and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at