NM_000455.5:c.929G>C

Variant names:

• chr19-1222993-G-C
• NM_000455.5:c.929G>C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_000455.5(STK11):​c.929G>C​(p.Arg310Pro) 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: 7.76

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 4 ACMG points.

• 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 rank	MANE	Protein	UniProt
STK11	NM_000455.5	c.929G>C	p.Arg310Pro	missense_variant	Exon 8 of 10	ENST00000326873.12	NP_000446.1
STK11	NM_001407255.1	c.929G>C	p.Arg310Pro	missense_variant	Exon 8 of 9		NP_001394184.1
STK11	NR_176325.1	n.2196G>C		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.929G>C	p.Arg310Pro	missense_variant	Exon 8 of 10	1	NM_000455.5	ENSP00000324856.6
STK11	ENST00000652231.1	c.929G>C	p.Arg310Pro	missense_variant	Exon 8 of 9			ENSP00000498804.1
STK11	ENST00000585748.3	c.557G>C	p.Arg186Pro	missense_variant	Exon 10 of 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	0.88
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.10
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.29	T;T
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.96	D;D
M_CAP	Pathogenic	0.35	D
MetaRNN	Pathogenic	0.85	D;D
MetaSVM	Uncertain	0.034	D
MutationAssessor	Benign	1.6	.;L
PrimateAI	Uncertain	0.78	T
PROVEAN	Uncertain	-2.8	.;D
REVEL	Pathogenic	0.70
Sift	Benign	0.13	.;T
Sift4G	Benign	0.24	T;T
Polyphen		0.85	.;P
Vest4		0.89
MutPred		0.44		Gain of glycosylation at R310 (P = 0.0092);Gain of glycosylation at R310 (P = 0.0092);
MVP		0.81
MPC		0.28
ClinPred		0.97	D
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.8
Varity_R		0.99
gMVP		0.90

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: chr19-1222992;