chr19-1207239-G-C

Variant names:

• chr19-1207239-G-C
• rs3764640
• NM_000455.5:c.290+36G>C

GermlineCancer (beta)

Variant summary

Our verdict is Likely benign.

-2 Likely Benign

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received -2 classification points (ACMG Germline Pathogenicity v2019). PM2BP4_Strong

The NM_000455.5(STK11):c.290+36G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a cumulative frequency of 0.000000709 (AC=1) in the gnomAD database across 1,410,246 control chromosomes (no homozygotes observed). The grpmax filtering allele frequency (95% CI) is 0.000000921. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: STK11 NM_000455.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.01
• Publications: 44 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, G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet
• familial ovarian cancer

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: ClinGen

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript:

Our verdict: Likely_benign. The variant received -2 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	PM2Absent/extremely low in population databases		Very rare in gnomAD for AD/XL gene (popmax AF < threshold/10) — PM2; GnomAD popmax AF = 0.000000921 — very rare for AD/XL gene (threshold 0.0001) — PM2 moderate.
	BP4Computational evidence suggests no impact		Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Strong).

Variant Effect in Transcripts

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

RefSeq Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	STK11 NM_000455.5	MANE Select	c.290+36G>C	intron	Intron 1 of 9	Prot: NP_000446.1 UniProt:
	STK11 NM_001407255.1		c.290+36G>C	intron	Intron 1 of 8	Prot: NP_001394184.1 UniProt:
	STK11 NR_176325.1		n.1426+36G>C	intron	Intron 1 of 10	Prot:

STK11 NM_000455.5

MANE Select

HGVSc / HGVSpc.290+36G>C

Exon rankIntron 1 of 9

intron

Prot: NP_000446.1UniProt: Q15831-1A0A0S2Z4D1

STK11 NM_001407255.1

HGVSc / HGVSpc.290+36G>C

Exon rankIntron 1 of 8

intron

Prot: NP_001394184.1UniProt: Q15831-2

STK11 NR_176325.1

HGVSc / HGVSpn.1426+36G>C

Exon rankIntron 1 of 10

intron

Prot:

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	STK11 ENST00000326873.12	TSL:1MANE Select	c.290+36G>C	intron	Intron 1 of 9	Prot: ENSP00000324856.6 UniProt:
	STK11 ENST00000652231.1		c.290+36G>C	intron	Intron 1 of 8	Prot: ENSP00000498804.1 UniProt:
	STK11 ENST00000585748.3	TSL:3	c.-82-11178G>C	intron	Intron 3 of 11	Prot: ENSP00000477641.2 UniProt:

STK11 ENST00000326873.12

TSL:1MANE Select

HGVSc / HGVSpc.290+36G>C

Exon rankIntron 1 of 9

intron

Prot: ENSP00000324856.6UniProt: Q15831-1

STK11 ENST00000652231.1

HGVSc / HGVSpc.290+36G>C

Exon rankIntron 1 of 8

intron

Prot: ENSP00000498804.1UniProt: Q15831-2

STK11 ENST00000585748.3

TSL:3

HGVSc / HGVSpc.-82-11178G>C

Exon rankIntron 3 of 11

intron

Prot: ENSP00000477641.2UniProt: A0A087WT72

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 3 sources Large-scale international reference populations
GnomAD3 genomes	AF:	AC:	Hom:	AN:	Cov:32
GnomAD4 exome	AF: 7.09e-7	AC:1	Hom:0	AN:1410246	Cov:33
GnomAD4 genome	AF:	AC:	Hom:	AN:	Cov:32

Showing 3 sources

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Benign	4.6
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.7
DANN	Benign	0.65
GPN-Star LLR	N/A	0.46
GPN-Star score	N/A	-0.46
PhyloP100	Benign	1.0
PromoterAI	N/A	0.012	Neutral

Showing 8 of 8 scores

Splicing Scores

Algorithm	Calibrated pred.	Score	Prediction
Pangolin (max)	Benign	0.0
SpliceAI score (max)	Benign	0.0	Details are displayed if max score is > 0.2

Showing 2 of 2 scores

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Other links and lift over

dbSNP: rs3764640;

hg19: chr19-1207238;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar