chr2-168159404-C-T

Variant names:

• chr2-168159404-C-T
• rs3754777
• NM_013233.3:c.628+2383G>A

Variant summary

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

The NM_013233.3(STK39):​c.628+2383G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 152,018 control chromosomes in the GnomAD database, including 2,104 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 0.16 (2104 hom., cov: 32)
• Consequence: STK39 NM_013233.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0330
• Publications: 40 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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.234 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STK39	NM_013233.3	c.628+2383G>A		intron_variant	Intron 5 of 17	ENST00000355999.5	NP_037365.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STK39	ENST00000355999.5	c.628+2383G>A		intron_variant	Intron 5 of 17	1	NM_013233.3	ENSP00000348278.4
STK39	ENST00000697205.1	c.628+2383G>A		intron_variant	Intron 5 of 16			ENSP00000513185.1

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24893 AN: 151900 Hom.: 2105 Cov.: 32

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.245

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.158

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.170

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

GnomAD4 genome AF: 0.164 AC: 24896 AN: 152018 Hom.: 2104 Cov.: 32 AF XY: 0.163 AC XY: 12120 AN XY: 74286

African (AFR) AF: 0.130 AC: 5403 AN: 41424

American (AMR) AF: 0.226 AC: 3454 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 503 AN: 3468

East Asian (EAS) AF: 0.246 AC: 1269 AN: 5166

South Asian (SAS) AF: 0.214 AC: 1028 AN: 4806

European-Finnish (FIN) AF: 0.158 AC: 1666 AN: 10568

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.163 AC: 11052 AN: 67990

Other (OTH) AF: 0.172 AC: 362 AN: 2108

Alfa AF: 0.160 Hom.: 1058

Bravo AF: 0.168

Asia WGS AF: 0.202 AC: 701 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	9.2
DANN	Benign	0.83
PhyloP100		0.033
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: rs3754777; hg19: chr2-169015914;