2-168247246-C-G

Variant names:

• chr2-168247246-C-G
• rs1440842849
• NM_013233.3:c.190G>C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_013233.3(STK39):​c.190G>C​(p.Glu64Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000953 in 1,153,772 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000041 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000050 (0 hom.)
• Consequence: STK39 NM_013233.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.97

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

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STK39	NM_013233.3	c.190G>C	p.Glu64Gln	missense_variant	Exon 1 of 18	ENST00000355999.5	NP_037365.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STK39	ENST00000355999.5	c.190G>C	p.Glu64Gln	missense_variant	Exon 1 of 18	1	NM_013233.3	ENSP00000348278.4
STK39	ENST00000697205.1	c.190G>C	p.Glu64Gln	missense_variant	Exon 1 of 17			ENSP00000513185.1

Frequencies

GnomAD3 genomes AF: 0.0000408 AC: 6 AN: 147062 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00120

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000497 AC: 5 AN: 1006710 Hom.: 0 Cov.: 28 AF XY: 0.00000619 AC XY: 3 AN XY: 484324

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000218

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000271

GnomAD4 genome AF: 0.0000408 AC: 6 AN: 147062 Hom.: 0 Cov.: 31 AF XY: 0.0000419 AC XY: 3 AN XY: 71626

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00120

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.34
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.17	T
Eigen	Uncertain	0.21
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Benign	0.71	D
LIST_S2	Uncertain	0.96	D
M_CAP	Pathogenic	0.83	D
MetaRNN	Uncertain	0.42	T
MetaSVM	Benign	-0.55	T
MutationAssessor	Benign	1.4	L
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.21
Sift	Benign	0.079	T
Sift4G	Benign	0.066	T
Polyphen		0.68	P
Vest4		0.28
MutPred		0.49		Gain of MoRF binding (P = 0.1042);
MVP		0.38
MPC		1.3
ClinPred		0.86	D
GERP RS		4.3
Varity_R		0.41
gMVP		0.34

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs1440842849; hg19: chr2-169103756;