Genetic Variant STK11:c.598-8C>A (chr19-1220573-C-A) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_000455.5(STK11):c.598-8C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

STK11
NM_000455.5 splice_region, intron

Scores

Splicing: ADA: 0.9817

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.207

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

familial pancreatic carcinoma
Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
Peutz-Jeghers syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp, Orphanet
familial ovarian cancer
Inheritance: Unknown Classification: NO_KNOWN Submitted by: ClinGen

STK11 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, max_spliceai. No scorers claiming Uncertain. Scorers claiming Benign: dbscSNV1_RF.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000455.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
STK11	NM_000455.5	MANE Select	c.598-8C>A	splice_region intron	N/A	NP_000446.1	A0A0S2Z4D1
STK11	NM_001407255.1		c.598-8C>A	splice_region intron	N/A	NP_001394184.1	Q15831-2
STK11	NR_176325.1		n.1865-8C>A	splice_region intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
STK11	ENST00000326873.12	TSL:1 MANE Select	c.598-8C>A	splice_region intron	N/A	ENSP00000324856.6	Q15831-1
STK11	ENST00000652231.1		c.598-8C>A	splice_region intron	N/A	ENSP00000498804.1	Q15831-2
STK11	ENST00000585748.3	TSL:3	c.226-8C>A	splice_region intron	N/A	ENSP00000477641.2	A0A087WT72

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1425154

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

704974

African (AFR)

AF:

0.00

AC:

AN:

32684

American (AMR)

AF:

0.00

AC:

AN:

40272

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25244

East Asian (EAS)

AF:

0.00

AC:

AN:

37914

South Asian (SAS)

AF:

0.00

AC:

AN:

82676

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5678

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1092362

Other (OTH)

AF:

0.00

AC:

AN:

58718

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

(source)

DANN

Benign

0.51

PhyloP100

-0.21

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

0.98

dbscSNV1_RF

Benign

0.45

SpliceAI score (max)

0.65

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.65

Position offset: 2

DS_AL_spliceai

0.41

Position offset: 8

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over