rs373096204

chr19-1221933-G-Achr19-1221933-G-Cchr19-1221933-G-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_000455.5(STK11):c.863-16G>A 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 0.0000277 in 1,551,482 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 0.000072 (0 hom., cov: 34)
  • Exomes 𝑓: 0.000023 (0 hom.)
• Consequence: STK11 NM_000455.5 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.77

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 19-1221933-G-A is Benign according to our data. Variant chr19-1221933-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 492565.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STK11	NM_000455.5	c.863-16G>A		splice_polypyrimidine_tract_variant, intron_variant		ENST00000326873.12
STK11	NM_001407255.1	c.863-16G>A		splice_polypyrimidine_tract_variant, intron_variant
STK11	NR_176325.1	n.2130-16G>A		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STK11	ENST00000326873.12	c.863-16G>A		splice_polypyrimidine_tract_variant, intron_variant		1	NM_000455.5	P1

Frequencies

GnomAD3 genomes AF: 0.0000723 AC: 11 AN: 152248 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000450 AC: 7 AN: 155398 Hom.: 0 AF XY: 0.0000363 AC XY: 3 AN XY: 82648

Gnomad AFR exome AF: 0.000501

Gnomad AMR exome AF: 0.0000402

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: 0.0000166

Gnomad OTH exome AF: 0.000229

GnomAD4 exome AF: 0.0000229 AC: 32 AN: 1399116 Hom.: 0 Cov.: 30 AF XY: 0.0000232 AC XY: 16 AN XY: 690310

Gnomad4 AFR exome AF: 0.000316

Gnomad4 AMR exome AF: 0.0000557

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000126

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000167

Gnomad4 OTH exome AF: 0.0000172

GnomAD4 genome AF: 0.0000722 AC: 11 AN: 152366 Hom.: 0 Cov.: 34 AF XY: 0.0000403 AC XY: 3 AN XY: 74512

Gnomad4 AFR AF: 0.000168

Gnomad4 AMR AF: 0.0000653

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000982

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Peutz-Jeghers syndrome Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -
Likely benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

Hereditary cancer-predisposing syndrome Benign:2

Benign, criteria provided, single submitter	curation	Sema4, Sema4	Sep 30, 2021	- -
Likely benign, criteria provided, single submitter	clinical testing	Color Diagnostics, LLC DBA Color Health	Sep 23, 2016	- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.12
Dann	Benign	0.57
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

Other links and lift over

dbSNP: rs373096204; hg19: chr19-1221932;