rs878853985

Variant names:

• chr19-1226590-C-A
• rs878853985
• NM_000455.5:c.1245C>A

Your query was ambiguous. Multiple possible variants found:

• chr19-1226590-C-A
• chr19-1226590-C-G
• chr19-1226590-C-T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 2P and 10B. PM2 BP4 BP6_Very_Strong BP7

The NM_000455.5(STK11):​c.1245C>A​(p.Arg415Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. R415R) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: STK11 NM_000455.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.43
• Publications: 0 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 -8 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3869154).
• BP6: Variant 19-1226590-C-A is Benign according to our data. Variant chr19-1226590-C-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 1634951.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.43 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STK11	NM_000455.5	c.1245C>A	p.Arg415Arg	synonymous_variant	Exon 9 of 10	ENST00000326873.12	NP_000446.1
STK11	NR_176325.1	n.2512C>A		non_coding_transcript_exon_variant	Exon 10 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STK11	ENST00000326873.12	c.1245C>A	p.Arg415Arg	synonymous_variant	Exon 9 of 10	1	NM_000455.5	ENSP00000324856.6
STK11	ENST00000585748.3	c.873C>A	p.Arg291Arg	synonymous_variant	Exon 11 of 12	3		ENSP00000477641.2
STK11	ENST00000593219.6	n.*1070C>A		non_coding_transcript_exon_variant	Exon 10 of 11	3		ENSP00000466610.1
STK11	ENST00000593219.6	n.*1070C>A		3_prime_UTR_variant	Exon 10 of 11	3		ENSP00000466610.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1419982 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 702914

African (AFR) AF: 0.00 AC: 0 AN: 32228

American (AMR) AF: 0.00 AC: 0 AN: 38742

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25416

East Asian (EAS) AF: 0.00 AC: 0 AN: 37076

South Asian (SAS) AF: 0.00 AC: 0 AN: 81028

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48836

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5326

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1092582

Other (OTH) AF: 0.00 AC: 0 AN: 58748

GnomAD4 genome Cov.: 33

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Peutz-Jeghers syndrome Benign:2

Mar 31, 2025

Myriad Genetics, Inc.

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing. -

Jun 16, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hereditary cancer-predisposing syndrome Benign:1

Sep 01, 2021

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.091	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	7.9
DANN	Benign	0.90
DEOGEN2	Benign	0.24	T
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.22	T
MetaRNN	Benign	0.39	T
MetaSVM	Benign	-1.0	T
PhyloP100		1.4
Sift4G	Benign	0.25	T
Vest4		0.56
MVP		0.65
ClinPred		0.18	T
GERP RS		-0.46
Mutation Taster		=100/0	polymorphism

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: rs878853985; hg19: chr19-1226589;