chr19-1207007-A-T

Variant names:

• chr19-1207007-A-T
• NM_000455.5:c.94A>T

Variant summary

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

The NM_000455.5(STK11):​c.94A>T​(p.Thr32Ser) 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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. T32T) has been classified as Benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: STK11 NM_000455.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.08

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=0.25141367).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STK11	NM_000455.5	c.94A>T	p.Thr32Ser	missense_variant	Exon 1 of 10	ENST00000326873.12	NP_000446.1
STK11	NM_001407255.1	c.94A>T	p.Thr32Ser	missense_variant	Exon 1 of 9		NP_001394184.1
STK11	NR_176325.1	n.1230A>T		non_coding_transcript_exon_variant	Exon 1 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STK11	ENST00000326873.12	c.94A>T	p.Thr32Ser	missense_variant	Exon 1 of 10	1	NM_000455.5	ENSP00000324856.6
STK11	ENST00000652231.1	c.94A>T	p.Thr32Ser	missense_variant	Exon 1 of 9			ENSP00000498804.1
STK11	ENST00000585748.3	c.-82-11410A>T		intron_variant	Intron 3 of 11	3		ENSP00000477641.2
STK11	ENST00000593219.5	n.94A>T		non_coding_transcript_exon_variant	Exon 1 of 4	3		ENSP00000466610.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	0.0084	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	23
DANN	Benign	0.95
DEOGEN2	Benign	0.23	T;T;T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.24
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.89	D;D;D
M_CAP	Benign	0.050	D
MetaRNN	Benign	0.25	T;T;T
MetaSVM	Benign	-0.65	T
MutationAssessor	Benign	1.6	.;L;.
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	0.45	.;N;.
REVEL	Benign	0.28
Sift	Benign	0.60	.;T;.
Sift4G	Benign	0.72	T;T;T
Polyphen		0.0070	.;B;.
Vest4		0.51
MutPred		0.31		Loss of catalytic residue at T32 (P = 0.0204);Loss of catalytic residue at T32 (P = 0.0204);Loss of catalytic residue at T32 (P = 0.0204);
MVP		0.75
MPC		0.90
ClinPred		0.84	D
GERP RS		1.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7
Varity_R		0.065
gMVP		0.69

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: chr19-1207006;