chr19-1221218-A-C

Position:

• chr19-1221218-A-C

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1 PM2 PP3_Moderate

The NM_000455.5(STK11):​c.740A>C​(p.Asn247Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: STK11 NM_000455.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.98

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 Likely_pathogenic. Variant got 6 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
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.848

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STK11	NM_000455.5	c.740A>C	p.Asn247Thr	missense_variant	6/10	ENST00000326873.12	NP_000446.1
STK11	NM_001407255.1	c.740A>C	p.Asn247Thr	missense_variant	6/9		NP_001394184.1
STK11	NR_176325.1	n.2007A>C		non_coding_transcript_exon_variant	7/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STK11	ENST00000326873.12	c.740A>C	p.Asn247Thr	missense_variant	6/10	1	NM_000455.5	ENSP00000324856.6
STK11	ENST00000652231.1	c.740A>C	p.Asn247Thr	missense_variant	6/9			ENSP00000498804.1
STK11	ENST00000585748.3	c.368A>C	p.Asn123Thr	missense_variant	8/12	3		ENSP00000477641.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.80
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.070
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.32	T;D
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.94	D;D
M_CAP	Uncertain	0.21	D
MetaRNN	Pathogenic	0.85	D;D
MetaSVM	Uncertain	-0.21	T
MutationAssessor	Benign	-0.23	.;N
PrimateAI	Pathogenic	0.89	D
PROVEAN	Pathogenic	-5.5	.;D
REVEL	Uncertain	0.61
Sift	Uncertain	0.0030	.;D
Sift4G	Benign	0.099	T;T
Polyphen		1.0	.;D
Vest4		0.91
MutPred		0.50		Gain of glycosylation at T249 (P = 0.1923);Gain of glycosylation at T249 (P = 0.1923);
MVP		0.78
MPC		2.1
ClinPred		0.99	D
GERP RS		4.5
Varity_R		0.89
gMVP		0.91

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: chr19-1221217;