rs1064795642

Positions:

• chr19-1206904-TG-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6 BS2

The NM_000455.5(STK11):​c.-7delG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000849 in 1,413,294 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000085 (0 hom.)
• Consequence: STK11 NM_000455.5 5_prime_UTR
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:3
• Conservation: PhyloP100: 1.12

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 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• BP6: Variant 19-1206904-TG-T is Benign according to our data. Variant chr19-1206904-TG-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 422225.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=3, Uncertain_significance=1}.
• BS2: High AC in GnomAdExome4 at 12 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STK11	NM_000455.5	c.-7delG		5_prime_UTR_variant	1/10	ENST00000326873.12	NP_000446.1
STK11	NM_001407255.1	c.-7delG		5_prime_UTR_variant	1/9		NP_001394184.1
STK11	NR_176325.1	n.1130delG		non_coding_transcript_exon_variant	1/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STK11	ENST00000326873	c.-7delG		5_prime_UTR_variant	1/10	1	NM_000455.5	ENSP00000324856.6
STK11	ENST00000652231	c.-7delG		5_prime_UTR_variant	1/9			ENSP00000498804.1
STK11	ENST00000585748.3	c.-82-11510delG		intron_variant		3		ENSP00000477641.2
STK11	ENST00000593219.5	n.-7delG		non_coding_transcript_exon_variant	1/4	3		ENSP00000466610.1
STK11	ENST00000593219.5	n.-7delG		5_prime_UTR_variant	1/4	3		ENSP00000466610.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000849 AC: 12 AN: 1413294 Hom.: 0 Cov.: 31 AF XY: 0.00000716 AC XY: 5 AN XY: 698414

Gnomad4 AFR exome AF: 0.00

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: 0.00

Gnomad4 NFE exome AF: 0.00000920

Gnomad4 OTH exome AF: 0.0000342

GnomAD4 genome Cov.: 31

Bravo AF: 0.0000113

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:3

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not specified Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	Jul 31, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 12, 2016	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. -

Peutz-Jeghers syndrome Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

St. Jude Molecular Pathology, St. Jude Children's Research Hospital

Sep 29, 2021

The STK11 c.-7del change deletes one nucleotide located 7 base pairs upstream of the ATG transcriptional start site in the 5’UTR of the STK11 gene. This deletion is not expected to create a new start codon and disrupt transcription, however the effect of this variant on protein function has not been confirmed by functional assays. This variant is absent in gnomAD v2.1.1 (PM2_Supporting; https://gnomad.broadinstitute.org/) and is not reported in a database of women older than 70 years of age who have never had cancer (FLOSSIES database, https://whi.color.com/). To our knowledge, this variant has not been reported in individuals with Peutz-Jeghers syndrome. In summary, this variant meets criteria to be classified as of uncertain significance based on the ACMG/AMP criteria: PM2_Supporting. -

Hereditary cancer-predisposing syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Color Diagnostics, LLC DBA Color Health

Jun 21, 2017

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs1064795642; hg19: chr19-1206903;