19-1223164-C-G

Variant names:

• chr19-1223164-C-G
• rs587782835
• NM_000455.5:c.1100C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000455.5(STK11):​c.1100C>G​(p.Thr367Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 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. T367M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: STK11 NM_000455.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.58
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24400577).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STK11	NM_000455.5	c.1100C>G	p.Thr367Arg	missense_variant	Exon 8 of 10	ENST00000326873.12	NP_000446.1
STK11	NM_001407255.1	c.1100C>G	p.Thr367Arg	missense_variant	Exon 8 of 9		NP_001394184.1
STK11	NR_176325.1	n.2367C>G		non_coding_transcript_exon_variant	Exon 9 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STK11	ENST00000326873.12	c.1100C>G	p.Thr367Arg	missense_variant	Exon 8 of 10	1	NM_000455.5	ENSP00000324856.6
STK11	ENST00000652231.1	c.1100C>G	p.Thr367Arg	missense_variant	Exon 8 of 9			ENSP00000498804.1
STK11	ENST00000585748.3	c.728C>G	p.Thr243Arg	missense_variant	Exon 10 of 12	3		ENSP00000477641.2
STK11	ENST00000593219.6	n.*925C>G		non_coding_transcript_exon_variant	Exon 9 of 11	3		ENSP00000466610.1
STK11	ENST00000593219.6	n.*925C>G		3_prime_UTR_variant	Exon 9 of 11	3		ENSP00000466610.1

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	Uncertain	0.42
BayesDel_addAF	Uncertain	0.097	D
BayesDel_noAF	Benign	-0.10
CADD	Benign	23
DANN	Benign	0.97
DEOGEN2	Benign	0.27	T;T;T
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.47	N
LIST_S2	Uncertain	0.92	D;D;T
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.24	T;T;T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	1.8	.;L;.
PhyloP100		5.6
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.37	.;N;.
REVEL	Uncertain	0.31
Sift	Benign	0.12	.;T;.
Sift4G	Benign	0.56	T;T;.
Polyphen		0.53	.;P;.
Vest4		0.46
MutPred		0.40		Gain of catalytic residue at T367 (P = 0.0394);Gain of catalytic residue at T367 (P = 0.0394);.;
MVP		0.83
MPC		0.18
ClinPred		0.74	D
GERP RS		2.6
PromoterAI		-0.070	Neutral
Varity_R		0.16
gMVP		0.41
Mutation Taster		=76/24	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: rs587782835; hg19: chr19-1223163;