chr11-8436118-A-C

Variant names:

• chr11-8436118-A-C
• rs1057520013
• NM_001352389.2:c.969T>G

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: STK33 NM_001352389.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.36
• Publications: 2 publications found

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]

STK33 Gene-Disease associations (from GenCC):

• spermatogenic failure 93

  Inheritance: AR Classification: LIMITED Submitted by: PanelApp Australia

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.958

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001352389.2. 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
	STK33	NM_001352389.2	MANE Select	c.969T>G	p.Phe323Leu	missense	Exon 13 of 16	NP_001339318.1	Q9BYT3-1
	STK33	NM_001289061.2		c.969T>G	p.Phe323Leu	missense	Exon 10 of 13	NP_001275990.1	Q9BYT3-1
	STK33	NM_001352387.2		c.969T>G	p.Phe323Leu	missense	Exon 11 of 14	NP_001339316.1	Q9BYT3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STK33	ENST00000687296.1	MANE Select	c.969T>G	p.Phe323Leu	missense	Exon 13 of 16	ENSP00000509322.1	Q9BYT3-1
	STK33	ENST00000315204.5	TSL:1	c.969T>G	p.Phe323Leu	missense	Exon 11 of 14	ENSP00000320754.1	Q9BYT3-1
	STK33	ENST00000447869.5	TSL:1	c.969T>G	p.Phe323Leu	missense	Exon 9 of 12	ENSP00000416750.1	Q9BYT3-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.052	D
MetaRNN	Pathogenic	0.96	D
MetaSVM	Benign	-0.71	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		1.4
PrimateAI	Uncertain	0.66	T
PROVEAN	Pathogenic	-5.5	D
REVEL	Uncertain	0.53
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.78
MutPred		0.88		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
Mutation Taster		=67/33	disease causing (ClinVar)

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