chr19-1219363-A-G

Variant names:

• chr19-1219363-A-G
• rs1045257509
• NM_000455.5:c.414A>G

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_000455.5(STK11):​c.414A>G​(p.Glu138Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000971 in 1,441,974 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000097 (0 hom.)
• Consequence: STK11 NM_000455.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 3.09
• Publications: 1 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: Labcorp Genetics (formerly Invitae), ClinGen, Orphanet, Genomics England PanelApp, G2P
• familial ovarian cancer

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 19-1219363-A-G is Benign according to our data. Variant chr19-1219363-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 379899.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=3.09 with no splicing effect.
• BS2: High AC in GnomAdExome4 at 14 AD gene.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STK11	NM_000455.5	MANE Select	c.414A>G	p.Glu138Glu	synonymous	Exon 3 of 10	NP_000446.1
	STK11	NM_001407255.1		c.414A>G	p.Glu138Glu	synonymous	Exon 3 of 9	NP_001394184.1
	STK11	NR_176325.1		n.1681A>G		non_coding_transcript_exon	Exon 4 of 11

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STK11	ENST00000326873.12	TSL:1 MANE Select	c.414A>G	p.Glu138Glu	synonymous	Exon 3 of 10	ENSP00000324856.6
	STK11	ENST00000652231.1		c.414A>G	p.Glu138Glu	synonymous	Exon 3 of 9	ENSP00000498804.1
	STK11	ENST00000585748.3	TSL:3	c.42A>G	p.Glu14Glu	synonymous	Exon 5 of 12	ENSP00000477641.2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD2 exomes AF: 0.00000442 AC: 1 AN: 226400 AF XY: 0.00000817

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000980

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000971 AC: 14 AN: 1441974 Hom.: 0 Cov.: 36 AF XY: 0.00000978 AC XY: 7 AN XY: 715858

African (AFR) AF: 0.00 AC: 0 AN: 33082

American (AMR) AF: 0.00 AC: 0 AN: 42842

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25604

East Asian (EAS) AF: 0.00 AC: 0 AN: 37788

South Asian (SAS) AF: 0.00 AC: 0 AN: 83238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50862

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5726

European-Non Finnish (NFE) AF: 0.0000118 AC: 13 AN: 1103352

Other (OTH) AF: 0.0000168 AC: 1 AN: 59480

GnomAD4 genome Cov.: 34

Alfa AF: 0.0000508 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Peutz-Jeghers syndrome (3)
-	-	2	Hereditary cancer-predisposing syndrome (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	14
DANN	Benign	0.57
PhyloP100		3.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs1045257509; hg19: chr19-1219362;