NM_000455.5:c.301C>T

Variant names:

• chr19-1218427-C-T
• rs587780716
• NM_000455.5:c.301C>T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM2 BP4_Strong BP6_Very_Strong

The NM_000455.5(STK11):​c.301C>T​(p.Leu101Leu) variant causes a synonymous change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: STK11 NM_000455.5 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 5.98

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 Benign. Variant got -10 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 19-1218427-C-T is Benign according to our data. Variant chr19-1218427-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 630726.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STK11	NM_000455.5	c.301C>T	p.Leu101Leu	synonymous_variant	Exon 2 of 10	ENST00000326873.12	NP_000446.1
STK11	NM_001407255.1	c.301C>T	p.Leu101Leu	synonymous_variant	Exon 2 of 9		NP_001394184.1
STK11	NR_176325.1	n.1568C>T		non_coding_transcript_exon_variant	Exon 3 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STK11	ENST00000326873.12	c.301C>T	p.Leu101Leu	synonymous_variant	Exon 2 of 10	1	NM_000455.5	ENSP00000324856.6
STK11	ENST00000652231.1	c.301C>T	p.Leu101Leu	synonymous_variant	Exon 2 of 9			ENSP00000498804.1
STK11	ENST00000585748	c.-72C>T		5_prime_UTR_variant	Exon 4 of 12	3		ENSP00000477641.2
STK11	ENST00000593219.5	n.*126C>T		non_coding_transcript_exon_variant	Exon 3 of 4	3		ENSP00000466610.1
STK11	ENST00000593219.5	n.*126C>T		3_prime_UTR_variant	Exon 3 of 4	3		ENSP00000466610.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Hereditary cancer-predisposing syndrome Benign:2

Oct 28, 2017

Color Diagnostics, LLC DBA Color Health

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 21, 2022

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Peutz-Jeghers syndrome Benign:1

Oct 31, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	6.1
DANN	Benign	0.92

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

LitVar

Other links and lift over

dbSNP: rs587780716; hg19: chr19-1218426;