rs528535500

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_000455.5(STK11):​c.537G>A​(p.Pro179Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,606,732 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

STK11
NM_000455.5 synonymous

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -2.57
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.92).
BP6
Variant 19-1220445-G-A is Benign according to our data. Variant chr19-1220445-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 187230.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-2.57 with no splicing effect.
BS2
High AC in GnomAdExome4 at 16 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
STK11NM_000455.5 linkc.537G>A p.Pro179Pro synonymous_variant Exon 4 of 10 ENST00000326873.12 NP_000446.1 Q15831-1A0A0S2Z4D1
STK11NM_001407255.1 linkc.537G>A p.Pro179Pro synonymous_variant Exon 4 of 9 NP_001394184.1
STK11NR_176325.1 linkn.1804G>A non_coding_transcript_exon_variant Exon 5 of 11

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
STK11ENST00000326873.12 linkc.537G>A p.Pro179Pro synonymous_variant Exon 4 of 10 1 NM_000455.5 ENSP00000324856.6 Q15831-1
STK11ENST00000652231.1 linkc.537G>A p.Pro179Pro synonymous_variant Exon 4 of 9 ENSP00000498804.1 Q15831-2
STK11ENST00000585748.3 linkc.165G>A p.Pro55Pro synonymous_variant Exon 6 of 12 3 ENSP00000477641.2 A0A087WT72

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152184
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000127
AC:
3
AN:
235520
Hom.:
0
AF XY:
0.0000156
AC XY:
2
AN XY:
128098
show subpopulations
Gnomad AFR exome
AF:
0.0000719
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000579
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000494
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000110
AC:
16
AN:
1454548
Hom.:
0
Cov.:
32
AF XY:
0.0000152
AC XY:
11
AN XY:
722950
show subpopulations
Gnomad4 AFR exome
AF:
0.0000599
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000193
Gnomad4 NFE exome
AF:
0.00000902
Gnomad4 OTH exome
AF:
0.0000333
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152184
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74340
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000151

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:11
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Peutz-Jeghers syndrome Benign:6
Oct 13, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Apr 12, 2023
Myriad Genetics, Inc.
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing. -

Jul 15, 2021
Genome-Nilou Lab
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Mar 26, 2018
Counsyl
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

-
Department of Pathology and Laboratory Medicine, Sinai Health System
Significance: Likely benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

The STK11 p.Pro179= variant was not identified in the literature nor was it identified in the LOVD 3.0, database. The variant was identified in dbSNP (rs528535500) as “with likely benign, other allele” and ClinVar (classified as likely benign by Invitae, Color, Ambry Genetics and 2 other submitters and benign by GeneDx). The variant was identified in control databases in 3 of 235,520 chromosomes at a frequency of 0.00001 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: African in 1 of 13,916 chromosomes (freq: 0.000072), East Asian in 1 of 17,286 chromosomes (freq: 0.00006), Finnish in 1 of 20,240 chromosomes (freq: 0.00005), while the variant was not observed in the Latino, Ashkenazi Jewish, European, Other and South Asian populations. The p.Pro179= variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. The variant occurs at a non-highly conserved nucleotide outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) 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. -

Jul 29, 2024
All of Us Research Program, National Institutes of Health
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Hereditary cancer-predisposing syndrome Benign:3
Apr 27, 2016
Color Diagnostics, LLC DBA Color Health
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Dec 02, 2014
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Mar 10, 2022
Sema4, Sema4
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: curation

- -

not specified Benign:1
Aug 14, 2015
GeneDx
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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. -

not provided Benign:1
Jan 16, 2023
Quest Diagnostics Nichols Institute San Juan Capistrano
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.92
CADD
Benign
0.097
DANN
Benign
0.91
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs528535500; hg19: chr19-1220444; API