chr19-1226597-T-G

Position:

• chr19-1226597-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000326873.12(STK11):​c.1252T>G​(p.Cys418Gly) 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. 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. C418S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: STK11 ENST00000326873.12 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.93

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23243988).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STK11	NM_000455.5	c.1252T>G	p.Cys418Gly	missense_variant	9/10	ENST00000326873.12	NP_000446.1
STK11	NR_176325.1	n.2519T>G		non_coding_transcript_exon_variant	10/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STK11	ENST00000326873.12	c.1252T>G	p.Cys418Gly	missense_variant	9/10	1	NM_000455.5	ENSP00000324856	P1

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	Benign	0.057
BayesDel_addAF	Benign	-0.066	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	23
DANN	Benign	0.93
DEOGEN2	Benign	0.41	T
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.54	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.042	D
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.5	L
MutationTaster	Benign	0.81	N
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.041
Sift	Uncertain	0.013	D
Sift4G	Benign	0.48	T
Polyphen		0.085	B
Vest4		0.48
MutPred		0.25		Loss of stability (P = 0.0114);
MVP		0.38
MPC		0.051
ClinPred		0.37	T
GERP RS		3.2
Varity_R		0.25
gMVP		0.26

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-1226596;