2-168145623-T-C

Variant names:

• chr2-168145623-T-C
• rs1517329
• NM_013233.3:c.629-4865A>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.629-4865A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 152,264 control chromosomes in the GnomAD database, including 1,720 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 0.14 (1720 hom., cov: 32)
• Consequence: STK39 NM_013233.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.221
• Publications: 4 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.236 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.629-4865A>G		intron	N/A	NP_037365.2
	STK39	NM_001410961.1		c.629-4865A>G		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.629-4865A>G		intron	N/A	ENSP00000348278.4
	STK39	ENST00000697205.1		c.629-4865A>G		intron	N/A	ENSP00000513185.1

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20588 AN: 152146 Hom.: 1723 Cov.: 32

Gnomad AFR AF: 0.0325

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.247

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.150

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

GnomAD4 genome AF: 0.135 AC: 20589 AN: 152264 Hom.: 1720 Cov.: 32 AF XY: 0.137 AC XY: 10169 AN XY: 74428

African (AFR) AF: 0.0324 AC: 1347 AN: 41554

American (AMR) AF: 0.215 AC: 3291 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 485 AN: 3472

East Asian (EAS) AF: 0.247 AC: 1279 AN: 5174

South Asian (SAS) AF: 0.222 AC: 1072 AN: 4828

European-Finnish (FIN) AF: 0.157 AC: 1670 AN: 10606

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.161 AC: 10971 AN: 68020

Other (OTH) AF: 0.152 AC: 321 AN: 2112

Alfa AF: 0.142 Hom.: 305

Bravo AF: 0.134

Asia WGS AF: 0.200 AC: 695 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.7
DANN	Benign	0.53
PhyloP100		0.22
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: rs1517329; hg19: chr2-169002133;