rs1159551738

Variant names:

• chr19-1206918-A-C
• rs1159551738
• NM_000455.5:c.5A>C

Your query was ambiguous. Multiple possible variants found:

• chr19-1206918-A-C
• chr19-1206918-A-G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_000455.5(STK11):​c.5A>C​(p.Glu2Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000112 in 1,427,712 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E2Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: STK11 NM_000455.5 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:7
• Conservation: PhyloP100: 4.70
• Publications: 2 publications found

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: Labcorp Genetics (formerly Invitae), ClinGen, Orphanet, Genomics England PanelApp, G2P
• familial ovarian cancer

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.28322032).
• BS2: High AC in GnomAdExome4 at 16 AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STK11	NM_000455.5	MANE Select	c.5A>C	p.Glu2Ala	missense	Exon 1 of 10	NP_000446.1
	STK11	NM_001407255.1		c.5A>C	p.Glu2Ala	missense	Exon 1 of 9	NP_001394184.1
	STK11	NR_176325.1		n.1141A>C		non_coding_transcript_exon	Exon 1 of 11

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STK11	ENST00000326873.12	TSL:1 MANE Select	c.5A>C	p.Glu2Ala	missense	Exon 1 of 10	ENSP00000324856.6
	STK11	ENST00000652231.1		c.5A>C	p.Glu2Ala	missense	Exon 1 of 9	ENSP00000498804.1
	STK11	ENST00000585748.3	TSL:3	c.-82-11499A>C		intron	N/A	ENSP00000477641.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000516 AC: 1 AN: 193850 AF XY: 0.00000948

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000119

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000112 AC: 16 AN: 1427712 Hom.: 0 Cov.: 31 AF XY: 0.00000848 AC XY: 6 AN XY: 707250

African (AFR) AF: 0.00 AC: 0 AN: 32732

American (AMR) AF: 0.00 AC: 0 AN: 39356

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25500

East Asian (EAS) AF: 0.00 AC: 0 AN: 37780

South Asian (SAS) AF: 0.00 AC: 0 AN: 82102

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50068

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5716

European-Non Finnish (NFE) AF: 0.0000137 AC: 15 AN: 1095378

Other (OTH) AF: 0.0000169 AC: 1 AN: 59080

GnomAD4 genome Cov.: 31

Alfa AF: 0.0000468 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	2	-	Hereditary cancer-predisposing syndrome (2)
-	2	-	not provided (2)
-	2	-	Peutz-Jeghers syndrome (2)
-	1	-	Melanoma, cutaneous malignant, susceptibility to, 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.079	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.31	T
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.24
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.0	N
PhyloP100		4.7
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.14
Sift	Uncertain	0.021	D
Sift4G	Uncertain	0.032	D
Polyphen		0.0010	B
Vest4		0.23
MutPred		0.24		Loss of catalytic residue at M1 (P = 0.0537)
MVP		0.68
MPC		1.1
ClinPred		0.23	T
GERP RS		2.7
PromoterAI		0.16	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.13
gMVP		0.51
Mutation Taster		=83/17	polymorphism

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

Other links and lift over

dbSNP: rs1159551738; hg19: chr19-1206917;