2-168167365-C-G

Variant names:

• chr2-168167365-C-G
• rs1688716670
• NM_013233.3:c.364G>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_013233.3(STK39):​c.364G>C​(p.Val122Leu) variant causes a missense change involving the alteration of a 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 Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: STK39 NM_013233.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.57
• Publications: 0 publications found

Genes affected

STK39 (HGNC:17717): (serine/threonine kinase 39) This gene encodes a serine/threonine kinase that is thought to function in the cellular stress response pathway. The kinase is activated in response to hypotonic stress, leading to phosphorylation of several cation-chloride-coupled cotransporters. The catalytically active kinase specifically activates the p38 MAP kinase pathway, and its interaction with p38 decreases upon cellular stress, suggesting that this kinase may serve as an intermediate in the response to cellular stress. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.854

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013233.3. 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
	STK39	NM_013233.3	MANE Select	c.364G>C	p.Val122Leu	missense	Exon 3 of 18	NP_037365.2	Q9UEW8-1
	STK39	NM_001410961.1		c.364G>C	p.Val122Leu	missense	Exon 3 of 17	NP_001397890.1	A0A8V8TKT5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STK39	ENST00000355999.5	TSL:1 MANE Select	c.364G>C	p.Val122Leu	missense	Exon 3 of 18	ENSP00000348278.4	Q9UEW8-1
	STK39	ENST00000952313.1		c.364G>C	p.Val122Leu	missense	Exon 3 of 19	ENSP00000622372.1
	STK39	ENST00000697205.1		c.364G>C	p.Val122Leu	missense	Exon 3 of 17	ENSP00000513185.1	A0A8V8TKT5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.36	T
Eigen	Uncertain	0.62
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.97	D
M_CAP	Benign	0.022	T
MetaRNN	Pathogenic	0.85	D
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.015	N
PhyloP100		7.6
PrimateAI	Pathogenic	0.89	D
PROVEAN	Uncertain	-2.9	D
REVEL	Uncertain	0.40
Sift	Benign	0.21	T
Sift4G	Benign	0.32	T
Polyphen		1.0	D
Vest4		0.78
MutPred		0.68		Loss of catalytic residue at V122 (P = 0.1663)
MVP		0.75
MPC		1.5
ClinPred		0.85	D
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.44
gMVP		0.72
Mutation Taster		=27/73	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1688716670; hg19: chr2-169023875;