2-168247246-C-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_013233.3(STK39):​c.190G>T​(p.Glu64*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000199 in 1,006,710 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000020 (0 hom.)
• Consequence: STK39 NM_013233.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.97
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.190G>T	p.Glu64*	stop_gained	Exon 1 of 18	NP_037365.2	Q9UEW8-1
	STK39	NM_001410961.1		c.190G>T	p.Glu64*	stop_gained	Exon 1 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.190G>T	p.Glu64*	stop_gained	Exon 1 of 18	ENSP00000348278.4	Q9UEW8-1
	STK39	ENST00000952313.1		c.190G>T	p.Glu64*	stop_gained	Exon 1 of 19	ENSP00000622372.1
	STK39	ENST00000697205.1		c.190G>T	p.Glu64*	stop_gained	Exon 1 of 17	ENSP00000513185.1	A0A8V8TKT5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000199 AC: 2 AN: 1006710 Hom.: 0 Cov.: 28 AF XY: 0.00000206 AC XY: 1 AN XY: 484324

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 19658

American (AMR) AF: 0.00 AC: 0 AN: 6722

Ashkenazi Jewish (ASJ) AF: 0.0000953 AC: 1 AN: 10492

East Asian (EAS) AF: 0.00 AC: 0 AN: 18354

South Asian (SAS) AF: 0.0000355 AC: 1 AN: 28142

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 12284

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2402

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 871742

Other (OTH) AF: 0.00 AC: 0 AN: 36914

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.53	D
BayesDel_noAF	Pathogenic	0.53
CADD	Pathogenic	41
DANN	Uncertain	1.0
Eigen	Pathogenic	0.81
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Benign	0.71	D
PhyloP100		2.0
Vest4		0.69
GERP RS		4.3
PromoterAI		-0.18	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=5/195	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs1440842849; hg19: chr2-169103756;