19-1223069-G-T

Position:

• chr19-1223069-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000455.5(STK11):​c.1005G>T​(p.Met335Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000000687 in 1,455,688 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: STK11 NM_000455.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.58

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STK11	NM_000455.5	c.1005G>T	p.Met335Ile	missense_variant	8/10	ENST00000326873.12	NP_000446.1
STK11	NM_001407255.1	c.1005G>T	p.Met335Ile	missense_variant	8/9		NP_001394184.1
STK11	NR_176325.1	n.2272G>T		non_coding_transcript_exon_variant	9/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STK11	ENST00000326873.12	c.1005G>T	p.Met335Ile	missense_variant	8/10	1	NM_000455.5	ENSP00000324856.6
STK11	ENST00000652231.1	c.1005G>T	p.Met335Ile	missense_variant	8/9			ENSP00000498804.1
STK11	ENST00000585748.3	c.633G>T	p.Met211Ile	missense_variant	10/12	3		ENSP00000477641.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455688 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 723546

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000253

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Uncertain	0.079	D
BayesDel_noAF	Benign	-0.12
CADD	Uncertain	25
DANN	Benign	0.97
DEOGEN2	Benign	0.35	T;D
Eigen	Benign	0.024
Eigen_PC	Benign	0.071
FATHMM_MKL	Benign	0.64	D
LIST_S2	Uncertain	0.96	D;D
M_CAP	Uncertain	0.18	D
MetaRNN	Uncertain	0.50	D;D
MetaSVM	Benign	-0.41	T
MutationAssessor	Benign	2.0	.;M
PrimateAI	Uncertain	0.65	T
PROVEAN	Uncertain	-2.6	.;D
REVEL	Uncertain	0.46
Sift	Benign	0.20	.;T
Sift4G	Benign	0.30	T;T
Polyphen		0.30	.;B
Vest4		0.65
MutPred		0.41		Loss of disorder (P = 0.0963);Loss of disorder (P = 0.0963);
MVP		0.62
MPC		0.072
ClinPred		0.85	D
GERP RS		3.8
Varity_R		0.62
gMVP		0.56

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: rs1555739243; hg19: chr19-1223068; COSMIC: COSV58827913; COSMIC: COSV58827913;