Variant chr19-1221935-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_000455.5(STK11):c.863-14C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000329 in 1,551,914 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 0.000079 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000028 ( 0 hom. )

Consequence

STK11
NM_000455.5 splice_polypyrimidine_tract, intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -2.82

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]

STK11 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 19-1221935-C-T is Benign according to our data. Variant chr19-1221935-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 378678.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 12 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
STK11	NM_000455.5 linkuse as main transcript	c.863-14C>T	splice_polypyrimidine_tract_variant, intron_variant	ENST00000326873.12	NP_000446.1
STK11	NM_001407255.1 linkuse as main transcript	c.863-14C>T	splice_polypyrimidine_tract_variant, intron_variant		NP_001394184.1
STK11	NR_176325.1 linkuse as main transcript	n.2130-14C>T	splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STK11	ENST00000326873.12 linkuse as main transcript	c.863-14C>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_000455.5	ENSP00000324856	P1	Q15831-1

Frequencies

GnomAD3 genomes

AF:

0.0000788

AC:

AN:

152242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

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:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000576

AC:

AN:

156172

Hom.:

AF XY:

0.0000722

AC XY:

AN XY:

83108

show subpopulations

Gnomad AFR exome

AF:

0.000124

Gnomad AMR exome

AF:

0.000120

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000898

Gnomad SAS exome

AF:

0.0000437

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000328

Gnomad OTH exome

AF:

0.000228

GnomAD4 exome

AF:

0.0000279

AC:

AN:

1399672

Hom.:

Cov.:

AF XY:

0.0000391

AC XY:

AN XY:

690640

show subpopulations

Gnomad4 AFR exome

AF:

0.0000632

Gnomad4 AMR exome

AF:

0.0000834

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000279

Gnomad4 SAS exome

AF:

0.0000504

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000213

Gnomad4 OTH exome

AF:

0.000103

GnomAD4 genome

AF:

0.0000788

AC:

AN:

152242

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000567

ClinVar

Significance: Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Peutz-Jeghers syndrome

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	KCCC/NGS Laboratory, Kuwait Cancer Control Center	Jul 07, 2023	- -
Likely benign, criteria provided, single submitter	clinical testing	All of Us Research Program, National Institutes of Health	Dec 01, 2023	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not specified

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	Aug 15, 2023	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 17, 2015	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. -

Malignant tumor of breast

Benign:1

Likely benign, no assertion criteria provided

clinical testing

Department of Pathology and Laboratory Medicine, Sinai Health System

The STK11 c.863-14C>T variant was not identified in the literature, nor was it identified in the Cosmic, LOVD 3.0, Zhejiang University Database, or Insight Hereditary Tumors databases. The variant was identified in dbSNP (ID: rs756001994 as "With Likely benign, Uncertain significance allele") and in ClinVar (2x as likely benign by GeneDx and Color Genomics). The variant was identified in control databases in 12 of 181762 chromosomes at a frequency of 0.00007 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: African in 4 of 16456 chromosomes (freq: 0.0002), Other in 1 of 4832 chromosomes (freq: 0.0002), Latino in 3 of 25082 chromosomes (freq: 0.0001), European in 2 of 73216 chromosomes (freq: 0.00003), East Asian in 1 of 12088 chromosomes (freq: 0.00008), and South Asian in 1 of 22908 chromosomes (freq: 0.00004), while the variant was not observed in the Ashkenazi Jewish or Finnish populations. The variant occurs 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. -

Hereditary cancer-predisposing syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Color Diagnostics, LLC DBA Color Health

Apr 18, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.076

DANN

Benign

0.55

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over