2-168228349-T-C

Variant names:

• chr2-168228349-T-C
• rs10176669
• NM_013233.3:c.208+18879A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013233.3(STK39):​c.208+18879A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.723 in 151,982 control chromosomes in the GnomAD database, including 40,303 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.72 (40303 hom., cov: 31)
• Consequence: STK39 NM_013233.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.976
• Publications: 10 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.793 is higher than 0.05.

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.208+18879A>G		intron	N/A	NP_037365.2	Q9UEW8-1
	STK39	NM_001410961.1		c.208+18879A>G		intron	N/A	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.208+18879A>G		intron	N/A	ENSP00000348278.4	Q9UEW8-1
	STK39	ENST00000952313.1		c.208+18879A>G		intron	N/A	ENSP00000622372.1
	STK39	ENST00000697205.1		c.208+18879A>G		intron	N/A	ENSP00000513185.1	A0A8V8TKT5

Frequencies

GnomAD3 genomes AF: 0.724 AC: 109878 AN: 151864 Hom.: 40284 Cov.: 31

Gnomad AFR AF: 0.616

Gnomad AMI AF: 0.758

Gnomad AMR AF: 0.695

Gnomad ASJ AF: 0.805

Gnomad EAS AF: 0.545

Gnomad SAS AF: 0.625

Gnomad FIN AF: 0.811

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.798

Gnomad OTH AF: 0.727

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.723 AC: 109942 AN: 151982 Hom.: 40303 Cov.: 31 AF XY: 0.722 AC XY: 53612 AN XY: 74268

African (AFR) AF: 0.615 AC: 25505 AN: 41438

American (AMR) AF: 0.695 AC: 10611 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.805 AC: 2795 AN: 3470

East Asian (EAS) AF: 0.544 AC: 2805 AN: 5156

South Asian (SAS) AF: 0.626 AC: 3019 AN: 4824

European-Finnish (FIN) AF: 0.811 AC: 8540 AN: 10536

Middle Eastern (MID) AF: 0.656 AC: 193 AN: 294

European-Non Finnish (NFE) AF: 0.798 AC: 54258 AN: 67970

Other (OTH) AF: 0.723 AC: 1528 AN: 2112

Alfa AF: 0.766 Hom.: 34057

Bravo AF: 0.712

Asia WGS AF: 0.565 AC: 1964 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.1
DANN	Benign	0.75
PhyloP100		-0.98
Mutation Taster		=100/0	polymorphism (auto)

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: rs10176669; hg19: chr2-169084859;