NM_000455.5:c.718_721delTCGG

Variant summary

Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1PM2PP5

The NM_000455.5(STK11):​c.718_721delTCGG​(p.Ser240LeufsTer46) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. S240S) has been classified as Benign. Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 33)

Consequence

STK11
NM_000455.5 frameshift

Scores

Not classified

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 9.86

Publications

1 publications found
Variant links:
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

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ACMG classification

Classification was made for transcript

Our verdict: Pathogenic. The variant received 11 ACMG points.

PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 19-1220698-TGGTC-T is Pathogenic according to our data. Variant chr19-1220698-TGGTC-T is described in ClinVar as [Pathogenic]. Clinvar id is 7441.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
STK11NM_000455.5 linkc.718_721delTCGG p.Ser240LeufsTer46 frameshift_variant Exon 5 of 10 ENST00000326873.12 NP_000446.1 Q15831-1A0A0S2Z4D1
STK11NM_001407255.1 linkc.718_721delTCGG p.Ser240LeufsTer46 frameshift_variant Exon 5 of 9 NP_001394184.1
STK11NR_176325.1 linkn.1985_1988delTCGG non_coding_transcript_exon_variant Exon 6 of 11

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
STK11ENST00000326873.12 linkc.718_721delTCGG p.Ser240LeufsTer46 frameshift_variant Exon 5 of 10 1 NM_000455.5 ENSP00000324856.6 Q15831-1
STK11ENST00000652231.1 linkc.718_721delTCGG p.Ser240LeufsTer46 frameshift_variant Exon 5 of 9 ENSP00000498804.1 Q15831-2
STK11ENST00000585748.3 linkc.346_349delTCGG p.Ser116LeufsTer46 frameshift_variant Exon 7 of 12 3 ENSP00000477641.2 A0A087WT72
STK11ENST00000593219.6 linkn.*543_*546delTCGG non_coding_transcript_exon_variant Exon 6 of 11 3 ENSP00000466610.1 K7EMR0
STK11ENST00000593219.6 linkn.*543_*546delTCGG 3_prime_UTR_variant Exon 6 of 11 3 ENSP00000466610.1 K7EMR0

Frequencies

GnomAD3 genomes
Cov.:
33
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Peutz-Jeghers syndrome Pathogenic:1
Jan 01, 1998
OMIM
Significance:Pathogenic
Review Status:no assertion criteria provided
Collection Method:literature only

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
9.9
Mutation Taster
=3/197
disease causing (ClinVar)

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.080
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs587776657; hg19: chr19-1220697; API