chr2-168159661-G-C

Variant names:

• chr2-168159661-G-C
• rs3754776
• NM_013233.3:c.628+2126C>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.628+2126C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 152,140 control chromosomes in the GnomAD database, including 2,313 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 (2313 hom., cov: 32)
• Consequence: STK39 NM_013233.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.424
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.253 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STK39	NM_013233.3	c.628+2126C>G		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+2126C>G		intron_variant	Intron 5 of 17	1	NM_013233.3	ENSP00000348278.4
STK39	ENST00000697205.1	c.628+2126C>G		intron_variant	Intron 5 of 16			ENSP00000513185.1

Frequencies

GnomAD3 genomes AF: 0.158 AC: 23999 AN: 152022 Hom.: 2305 Cov.: 32

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.0879

Gnomad AMR AF: 0.166

Gnomad ASJ AF: 0.0880

Gnomad EAS AF: 0.210

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.150

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.0972

Gnomad OTH AF: 0.160

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

GnomAD4 genome AF: 0.158 AC: 24023 AN: 152140 Hom.: 2313 Cov.: 32 AF XY: 0.163 AC XY: 12096 AN XY: 74360

African (AFR) AF: 0.257 AC: 10653 AN: 41504

American (AMR) AF: 0.166 AC: 2533 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0880 AC: 305 AN: 3464

East Asian (EAS) AF: 0.209 AC: 1082 AN: 5166

South Asian (SAS) AF: 0.162 AC: 781 AN: 4816

European-Finnish (FIN) AF: 0.150 AC: 1588 AN: 10580

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.0973 AC: 6614 AN: 68006

Other (OTH) AF: 0.161 AC: 340 AN: 2116

Alfa AF: 0.0491 Hom.: 48

Bravo AF: 0.164

Asia WGS AF: 0.229 AC: 796 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.38
DANN	Benign	0.34
PhyloP100		-0.42
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: rs3754776; hg19: chr2-169016171;