rs1057520013

Positions:

• chr11-8436118-A-C

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2 PP3_Strong PP5

The NM_001352389.2(STK33):​c.969T>G​(p.Phe323Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: STK33 NM_001352389.2 missense
• Clinical Significance: Likely pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 1.36

Genes affected

STK33 (HGNC:14568): (serine/threonine kinase 33) Predicted to enable protein serine/threonine kinase activity. Predicted to be involved in mitotic DNA damage checkpoint signaling and protein autophosphorylation. Predicted to be located in perinuclear region of cytoplasm. Predicted to be active in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.958
• PP5: Variant 11-8436118-A-C is Pathogenic according to our data. Variant chr11-8436118-A-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 376702.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STK33	NM_001352389.2	c.969T>G	p.Phe323Leu	missense_variant	13/16	ENST00000687296.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STK33	ENST00000687296.1	c.969T>G	p.Phe323Leu	missense_variant	13/16		NM_001352389.2	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Neoplasm of the pancreas Pathogenic:1

Likely pathogenic, no assertion criteria provided

literature only

Database of Curated Mutations (DoCM)

May 13, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.070
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T;T;T;T;.;T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.78	.;.;T;T;T;T
M_CAP	Benign	0.052	D
MetaRNN	Pathogenic	0.96	D;D;D;D;D;D
MetaSVM	Benign	-0.71	T
MutationAssessor	Uncertain	2.2	M;M;M;.;.;.
MutationTaster	Benign	1.0	D;D;D;D;D;D
PrimateAI	Uncertain	0.66	T
PROVEAN	Pathogenic	-5.5	D;D;D;D;D;D
REVEL	Uncertain	0.53
Sift	Pathogenic	0.0	D;D;D;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D;D;D
Polyphen		1.0	D;D;D;.;.;D
Vest4		0.78
MutPred		0.88		Gain of disorder (P = 0.0638);Gain of disorder (P = 0.0638);Gain of disorder (P = 0.0638);.;.;.;
MVP		0.57
MPC		0.38
ClinPred		1.0	D
GERP RS		4.8
Varity_R		0.86
gMVP		0.83

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

Publications

LitVar

Other links and lift over

dbSNP: rs1057520013; hg19: chr11-8457665; COSMIC: COSV59398461; COSMIC: COSV59398461;