NM_000455.5:c.-1024C>T

Variant names:

• chr19-1205890-C-T
• rs147615524
• NM_000455.5:c.-1024C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000455.5(STK11):​c.-1024C>T variant causes a 5 prime UTR premature start codon gain 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_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.200
• Publications: 6 publications found

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: ClinGen, Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp, Orphanet
• familial ovarian cancer

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000455.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STK11	NM_000455.5	MANE Select	c.-1024C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 10	NP_000446.1	A0A0S2Z4D1
	STK11	NM_000455.5	MANE Select	c.-1024C>T		5_prime_UTR	Exon 1 of 10	NP_000446.1	A0A0S2Z4D1
	STK11	NM_001407255.1		c.-1024C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 9	NP_001394184.1	Q15831-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STK11	ENST00000326873.12	TSL:1 MANE Select	c.-1024C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 10	ENSP00000324856.6	Q15831-1
	STK11	ENST00000326873.12	TSL:1 MANE Select	c.-1024C>T		5_prime_UTR	Exon 1 of 10	ENSP00000324856.6	Q15831-1
	STK11	ENST00000585748.3	TSL:3	c.-82-12527C>T		intron	N/A	ENSP00000477641.2	A0A087WT72

Frequencies

GnomAD3 genomes AF: 0.0152 AC: 2282 AN: 150582 Hom.: 59 Cov.: 32

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

African (AFR) AF: 0.0630 AC: 108 AN: 1714

American (AMR) AF: 0.00823 AC: 9 AN: 1094

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2512

East Asian (EAS) AF: 0.00 AC: 0 AN: 6958

South Asian (SAS) AF: 0.00 AC: 0 AN: 416

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 22

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 258

European-Non Finnish (NFE) AF: 0.000165 AC: 4 AN: 24262

Other (OTH) AF: 0.00689 AC: 23 AN: 3338

GnomAD4 genome AF: 0.0152 AC: 2292 AN: 150690 Hom.: 59 Cov.: 32 AF XY: 0.0153 AC XY: 1124 AN XY: 73604

African (AFR) AF: 0.0531 AC: 2191 AN: 41264

American (AMR) AF: 0.00409 AC: 62 AN: 15144

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3460

East Asian (EAS) AF: 0.00 AC: 0 AN: 5122

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10048

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.000192 AC: 13 AN: 67536

Other (OTH) AF: 0.0124 AC: 26 AN: 2094

Alfa AF: 0.0126 Hom.: 7

Bravo AF: 0.0173

Asia WGS AF: 0.00179 AC: 6 AN: 3374

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	Peutz-Jeghers syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	12
DANN	Benign	0.96
PhyloP100		0.20
PromoterAI		0.049	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.3
Mutation Taster		=300/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs147615524; hg19: chr19-1205889;