rs1006375117

chr19-1219380-C-Achr19-1219380-C-Gchr19-1219380-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM1

The NM_000455.5(STK11):c.431C>A(p.Pro144Gln) variant causes a missense change. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P144L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: STK11 NM_000455.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.79

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 hotspot region, there are 2 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 15 uncertain in NM_000455.5

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STK11	NM_000455.5	c.431C>A	p.Pro144Gln	missense_variant	3/10	ENST00000326873.12
STK11	NM_001407255.1	c.431C>A	p.Pro144Gln	missense_variant	3/9
STK11	NR_176325.1	n.1698C>A		non_coding_transcript_exon_variant	4/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STK11	ENST00000326873.12	c.431C>A	p.Pro144Gln	missense_variant	3/10	1	NM_000455.5	P1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1350360 Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0 AN XY: 669944

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

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.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.034	T
BayesDel_noAF	Benign	-0.29
Cadd	Uncertain	24
Dann	Benign	0.97
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.055
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.82	T;D;D
M_CAP	Benign	0.040	D
MetaRNN	Uncertain	0.45	T;T;T
MetaSVM	Benign	-0.97	T
MutationTaster	Benign	1.0	D
PrimateAI	Pathogenic	0.81	D
Polyphen		0.27	.;.;B
Vest4		0.55, 0.59
MutPred		0.50		.;Gain of ubiquitination at K146 (P = 0.1162);Gain of ubiquitination at K146 (P = 0.1162);
MVP		0.56
MPC		0.94
ClinPred		0.92	D
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
Varity_R		0.51
gMVP		0.61

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: chr19-1219379;