rs6740826

Variant names:

• chr2-168171045-G-A
• rs6740826
• NM_013233.3:c.322-3638C>T

Variant summary

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

The NM_013233.3(STK39):​c.322-3638C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 152,142 control chromosomes in the GnomAD database, including 2,752 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 0.17 (2752 hom., cov: 32)
• Consequence: STK39 NM_013233.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.447
• Publications: 8 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.291 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STK39	NM_013233.3	MANE Select	c.322-3638C>T		intron	N/A	NP_037365.2
	STK39	NM_001410961.1		c.322-3638C>T		intron	N/A	NP_001397890.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STK39	ENST00000355999.5	TSL:1 MANE Select	c.322-3638C>T		intron	N/A	ENSP00000348278.4
	STK39	ENST00000697205.1		c.322-3638C>T		intron	N/A	ENSP00000513185.1

Frequencies

GnomAD3 genomes AF: 0.169 AC: 25660 AN: 152024 Hom.: 2744 Cov.: 32

Gnomad AFR AF: 0.296

Gnomad AMI AF: 0.0857

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.0884

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.150

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.0971

Gnomad OTH AF: 0.165

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

GnomAD4 genome AF: 0.169 AC: 25682 AN: 152142 Hom.: 2752 Cov.: 32 AF XY: 0.173 AC XY: 12875 AN XY: 74386

African (AFR) AF: 0.295 AC: 12251 AN: 41496

American (AMR) AF: 0.169 AC: 2590 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0884 AC: 307 AN: 3472

East Asian (EAS) AF: 0.209 AC: 1079 AN: 5168

South Asian (SAS) AF: 0.162 AC: 782 AN: 4824

European-Finnish (FIN) AF: 0.150 AC: 1591 AN: 10596

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.0971 AC: 6605 AN: 67988

Other (OTH) AF: 0.166 AC: 351 AN: 2112

Alfa AF: 0.121 Hom.: 2707

Bravo AF: 0.176

Asia WGS AF: 0.231 AC: 801 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.6
DANN	Benign	0.52
PhyloP100		-0.45
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: rs6740826; hg19: chr2-169027555;