19-1221294-C-T

Variant names:

• chr19-1221294-C-T
• rs9282859
• NM_000455.5:c.816C>T

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_000455.5(STK11):​c.816C>T​(p.Tyr272Tyr) variant causes a synonymous change. The variant allele was found at a frequency of 0.00467 in 1,611,214 control chromosomes in the GnomAD database, including 280 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.024 (128 hom., cov: 33)
  • Exomes 𝑓: 0.0027 (152 hom.)
• Consequence: STK11 NM_000455.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:20
• Conservation: PhyloP100: 4.07
• Publications: 22 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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP6: Variant 19-1221294-C-T is Benign according to our data. Variant chr19-1221294-C-T is described in ClinVar as Benign. ClinVar VariationId is 141192.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.079 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.816C>T	p.Tyr272Tyr	synonymous	Exon 6 of 10	NP_000446.1	A0A0S2Z4D1
	STK11	NM_001407255.1		c.816C>T	p.Tyr272Tyr	synonymous	Exon 6 of 9	NP_001394184.1	Q15831-2
	STK11	NR_176325.1		n.2083C>T		non_coding_transcript_exon	Exon 7 of 11

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STK11	ENST00000326873.12	TSL:1 MANE Select	c.816C>T	p.Tyr272Tyr	synonymous	Exon 6 of 10	ENSP00000324856.6	Q15831-1
	STK11	ENST00000652231.1		c.816C>T	p.Tyr272Tyr	synonymous	Exon 6 of 9	ENSP00000498804.1	Q15831-2
	STK11	ENST00000585748.3	TSL:3	c.444C>T	p.Tyr148Tyr	synonymous	Exon 8 of 12	ENSP00000477641.2	A0A087WT72

Frequencies

GnomAD3 genomes AF: 0.0239 AC: 3630 AN: 152194 Hom.: 129 Cov.: 33

Gnomad AFR AF: 0.0814

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0112

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000412

Gnomad OTH AF: 0.0201

GnomAD2 exomes AF: 0.00581 AC: 1422 AN: 244572 AF XY: 0.00432

Gnomad AFR exome AF: 0.0820

Gnomad AMR exome AF: 0.00401

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000317

Gnomad OTH exome AF: 0.00269

GnomAD4 exome AF: 0.00267 AC: 3889 AN: 1458902 Hom.: 152 Cov.: 31 AF XY: 0.00230 AC XY: 1670 AN XY: 725584

African (AFR) AF: 0.0884 AC: 2960 AN: 33466

American (AMR) AF: 0.00467 AC: 208 AN: 44524

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26084

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39664

South Asian (SAS) AF: 0.000221 AC: 19 AN: 85910

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52132

Middle Eastern (MID) AF: 0.00642 AC: 37 AN: 5762

European-Non Finnish (NFE) AF: 0.000275 AC: 305 AN: 1111072

Other (OTH) AF: 0.00592 AC: 357 AN: 60288

GnomAD4 genome AF: 0.0239 AC: 3638 AN: 152312 Hom.: 128 Cov.: 33 AF XY: 0.0231 AC XY: 1719 AN XY: 74474

African (AFR) AF: 0.0813 AC: 3381 AN: 41568

American (AMR) AF: 0.0112 AC: 171 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5188

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000412 AC: 28 AN: 68008

Other (OTH) AF: 0.0199 AC: 42 AN: 2114

Alfa AF: 0.0147 Hom.: 47

Bravo AF: 0.0276

Asia WGS AF: 0.00433 AC: 16 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	7	not specified (7)
-	-	5	Peutz-Jeghers syndrome (5)
-	-	3	Hereditary cancer-predisposing syndrome (3)
-	-	3	not provided (3)
-	-	1	Breast and/or ovarian cancer (1)
-	-	1	Malignant tumor of breast (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	13
DANN	Benign	0.95
PhyloP100		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9282859; hg19: chr19-1221293; COSMIC: COSV58823633;