rs376069854
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7
The NM_000455.5(STK11):c.1107C>A(p.Pro369Pro) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,956 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P369P) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 6.9e-7 ( 0 hom. )
Consequence
STK11
NM_000455.5 splice_region, synonymous
NM_000455.5 splice_region, synonymous
Scores
2
Splicing: ADA: 0.00002700
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.242
Publications
0 publications found
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]
STK11 Gene-Disease associations (from GenCC):
- familial pancreatic carcinomaInheritance: AD Classification: DEFINITIVE Submitted by: G2P
- Peutz-Jeghers syndromeInheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Orphanet, Genomics England PanelApp, G2P
- familial ovarian cancerInheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
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ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.58).
BP7
Synonymous conserved (PhyloP=-0.242 with no splicing effect.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| STK11 | NM_000455.5 | c.1107C>A | p.Pro369Pro | splice_region_variant, synonymous_variant | Exon 8 of 10 | ENST00000326873.12 | NP_000446.1 | |
| STK11 | NM_001407255.1 | c.1107C>A | p.Pro369Pro | splice_region_variant, synonymous_variant | Exon 8 of 9 | NP_001394184.1 | ||
| STK11 | NR_176325.1 | n.2374C>A | splice_region_variant, non_coding_transcript_exon_variant | Exon 9 of 11 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| STK11 | ENST00000326873.12 | c.1107C>A | p.Pro369Pro | splice_region_variant, synonymous_variant | Exon 8 of 10 | 1 | NM_000455.5 | ENSP00000324856.6 | ||
| STK11 | ENST00000652231.1 | c.1107C>A | p.Pro369Pro | splice_region_variant, synonymous_variant | Exon 8 of 9 | ENSP00000498804.1 | ||||
| STK11 | ENST00000585748.3 | c.735C>A | p.Pro245Pro | splice_region_variant, synonymous_variant | Exon 10 of 12 | 3 | ENSP00000477641.2 | |||
| STK11 | ENST00000593219.6 | n.*932C>A | splice_region_variant, non_coding_transcript_exon_variant | Exon 9 of 11 | 3 | ENSP00000466610.1 | ||||
| STK11 | ENST00000593219.6 | n.*932C>A | 3_prime_UTR_variant | Exon 9 of 11 | 3 | ENSP00000466610.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD4 exome AF: 6.86e-7 AC: 1AN: 1457956Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 725026 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
1
AN:
1457956
Hom.:
Cov.:
31
AF XY:
AC XY:
1
AN XY:
725026
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
33460
American (AMR)
AF:
AC:
1
AN:
44526
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26048
East Asian (EAS)
AF:
AC:
0
AN:
39598
South Asian (SAS)
AF:
AC:
0
AN:
85788
European-Finnish (FIN)
AF:
AC:
0
AN:
51482
Middle Eastern (MID)
AF:
AC:
0
AN:
5758
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1111042
Other (OTH)
AF:
AC:
0
AN:
60254
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.225
Heterozygous variant carriers
0
0
1
1
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2
0.00
0.20
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0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
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10
<30
30-35
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>80
Age
GnomAD4 genome
GnomAD4 genome
Cov.:
33
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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