chr19-1220389-A-C

Variant names:

• chr19-1220389-A-C
• NM_000455.5:c.481A>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1 PM2 BP4_Moderate

The NM_000455.5(STK11):​c.481A>C​(p.Ile161Leu) variant causes a missense 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: STK11 NM_000455.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.32

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 Uncertain_significance. Variant got 2 ACMG points.

• PM1: In a domain Protein kinase (size 260) in uniprot entity STK11_HUMAN there are 19 pathogenic changes around while only 5 benign (79%) in NM_000455.5
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08712283).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STK11	NM_000455.5	c.481A>C	p.Ile161Leu	missense_variant	Exon 4 of 10	ENST00000326873.12	NP_000446.1
STK11	NM_001407255.1	c.481A>C	p.Ile161Leu	missense_variant	Exon 4 of 9		NP_001394184.1
STK11	NR_176325.1	n.1748A>C		non_coding_transcript_exon_variant	Exon 5 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STK11	ENST00000326873.12	c.481A>C	p.Ile161Leu	missense_variant	Exon 4 of 10	1	NM_000455.5	ENSP00000324856.6
STK11	ENST00000652231.1	c.481A>C	p.Ile161Leu	missense_variant	Exon 4 of 9			ENSP00000498804.1
STK11	ENST00000585748.3	c.109A>C	p.Ile37Leu	missense_variant	Exon 6 of 12	3		ENSP00000477641.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 04, 2025

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	16
DANN	Benign	0.88
DEOGEN2	Benign	0.23	T;T;T
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.59
FATHMM_MKL	Benign	0.45	N
LIST_S2	Uncertain	0.86	D;D;D
M_CAP	Benign	0.045	D
MetaRNN	Benign	0.087	T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-0.74	.;N;.
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.29	.;N;.
REVEL	Benign	0.16
Sift	Benign	0.71	.;T;.
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0	.;B;.
Vest4		0.35
MutPred		0.59		Loss of stability (P = 0.2921);Loss of stability (P = 0.2921);.;
MVP		0.27
MPC		0.99
ClinPred		0.049	T
GERP RS		3.5
Varity_R		0.26
gMVP		0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-1220388;