chr19-1219429-AG-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_000455.5(STK11):​c.464+20delG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000902 in 865,172 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.000022 ( 0 hom., cov: 34)
Exomes 𝑓: 0.00010 ( 1 hom. )

Consequence

STK11
NM_000455.5 intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.124
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 -16 ACMG points.

BP6
Variant 19-1219429-AG-A is Benign according to our data. Variant chr19-1219429-AG-A is described in ClinVar as [Likely_benign]. Clinvar id is 182879.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.000103 (75/726494) while in subpopulation AMR AF= 0.00222 (68/30670). AF 95% confidence interval is 0.00179. There are 1 homozygotes in gnomad4_exome. There are 30 alleles in male gnomad4_exome subpopulation. Median coverage is 45. This position pass quality control queck.
BS2
High AC in GnomAdExome4 at 75 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
STK11NM_000455.5 linkc.464+20delG intron_variant Intron 3 of 9 ENST00000326873.12 NP_000446.1 Q15831-1A0A0S2Z4D1
STK11NM_001407255.1 linkc.464+20delG intron_variant Intron 3 of 8 NP_001394184.1
STK11NR_176325.1 linkn.1731+20delG intron_variant Intron 4 of 10

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
STK11ENST00000326873.12 linkc.464+17delG intron_variant Intron 3 of 9 1 NM_000455.5 ENSP00000324856.6 Q15831-1
STK11ENST00000652231.1 linkc.464+17delG intron_variant Intron 3 of 8 ENSP00000498804.1 Q15831-2
STK11ENST00000585748.3 linkc.92+17delG intron_variant Intron 5 of 11 3 ENSP00000477641.2 A0A087WT72

Frequencies

GnomAD3 genomes
AF:
0.0000216
AC:
3
AN:
138678
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000142
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:
0.0000156
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000376
AC:
64
AN:
170296
Hom.:
1
AF XY:
0.000317
AC XY:
29
AN XY:
91418
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00171
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000143
Gnomad OTH exome
AF:
0.00388
GnomAD4 exome
AF:
0.000103
AC:
75
AN:
726494
Hom.:
1
Cov.:
45
AF XY:
0.0000810
AC XY:
30
AN XY:
370290
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00222
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000192
Gnomad4 OTH exome
AF:
0.000211
GnomAD4 genome
AF:
0.0000216
AC:
3
AN:
138678
Hom.:
0
Cov.:
34
AF XY:
0.0000149
AC XY:
1
AN XY:
67234
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000142
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000156
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000142
Hom.:
0
Bravo
AF:
0.0000680

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Peutz-Jeghers syndrome Benign:3
Likely benign, criteria provided, single submitterclinical testingGenome-Nilou LabJul 15, 2021- -
Likely benign, criteria provided, single submitterclinical testingCounsylSep 06, 2016- -
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpFeb 02, 2025- -
Hereditary cancer-predisposing syndrome Benign:2
Benign, criteria provided, single submitterclinical testingGeneDxAug 21, 2014The variant is found in HEREDICANCER,BR-OV-HEREDIC panel(s). -
Benign, criteria provided, single submitterclinical testingColor Diagnostics, LLC DBA Color HealthAug 31, 2016- -
not specified Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesDec 20, 2017- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs730881960; hg19: chr19-1219428; API