chr19-1205890-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000455.5(STK11):​c.-1024C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0127 in 191,264 control chromosomes in the GnomAD database, including 61 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 59 hom., cov: 32)
Exomes 𝑓: 0.0035 ( 2 hom. )

Consequence

STK11
NM_000455.5 5_prime_UTR

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.200
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.71).
BP6
Variant 19-1205890-C-T is Benign according to our data. Variant chr19-1205890-C-T is described in ClinVar as [Benign]. Clinvar id is 328204.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0512 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
STK11NM_000455.5 linkuse as main transcriptc.-1024C>T 5_prime_UTR_variant 1/10 ENST00000326873.12 NP_000446.1
STK11NM_001407255.1 linkuse as main transcriptc.-1024C>T 5_prime_UTR_variant 1/9 NP_001394184.1
STK11NR_176325.1 linkuse as main transcriptn.113C>T non_coding_transcript_exon_variant 1/11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
STK11ENST00000326873.12 linkuse as main transcriptc.-1024C>T 5_prime_UTR_variant 1/101 NM_000455.5 ENSP00000324856 P1Q15831-1
STK11ENST00000585465.3 linkuse as main transcriptc.-1024C>T 5_prime_UTR_variant 1/105 ENSP00000490268
STK11ENST00000585748.3 linkuse as main transcriptc.-82-12527C>T intron_variant 3 ENSP00000477641

Frequencies

GnomAD3 genomes
AF:
0.0152
AC:
2282
AN:
150582
Hom.:
59
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0530
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00410
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000192
Gnomad OTH
AF:
0.0121
GnomAD4 exome
AF:
0.00355
AC:
144
AN:
40574
Hom.:
2
Cov.:
0
AF XY:
0.00370
AC XY:
70
AN XY:
18914
show subpopulations
Gnomad4 AFR exome
AF:
0.0630
Gnomad4 AMR exome
AF:
0.00823
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000165
Gnomad4 OTH exome
AF:
0.00689
GnomAD4 genome
AF:
0.0152
AC:
2292
AN:
150690
Hom.:
59
Cov.:
32
AF XY:
0.0153
AC XY:
1124
AN XY:
73604
show subpopulations
Gnomad4 AFR
AF:
0.0531
Gnomad4 AMR
AF:
0.00409
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000192
Gnomad4 OTH
AF:
0.0124
Alfa
AF:
0.0126
Hom.:
7
Bravo
AF:
0.0173
Asia WGS
AF:
0.00179
AC:
6
AN:
3374

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxJul 26, 2019- -
Peutz-Jeghers syndrome Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.71
CADD
Benign
12
DANN
Benign
0.96
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.3

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs147615524; hg19: chr19-1205889; API