rs56031549

Variant names:

• chr2-168075126-C-T
• rs56031549
• NM_013233.3:c.1195G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_013233.3(STK39):​c.1195G>A​(p.Ala399Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0126 in 1,614,172 control chromosomes in the GnomAD database, including 161 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 0.011 (13 hom., cov: 32)
  • Exomes 𝑓: 0.013 (148 hom.)
• Consequence: STK39 NM_013233.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.01

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 (MetaRNN=0.006496787).
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.0114 (1734/152290) while in subpopulation AMR AF = 0.0191 (292/15306). AF 95% confidence interval is 0.0173. There are 13 homozygotes in GnomAd4. There are 831 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position FAILED quality control check.
• BS2: High AC in GnomAd4 at 1734 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STK39	NM_013233.3	c.1195G>A	p.Ala399Thr	missense_variant	Exon 11 of 18	ENST00000355999.5	NP_037365.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STK39	ENST00000355999.5	c.1195G>A	p.Ala399Thr	missense_variant	Exon 11 of 18	1	NM_013233.3	ENSP00000348278.4
STK39	ENST00000487143.5	n.295G>A		non_coding_transcript_exon_variant	Exon 2 of 9	1
STK39	ENST00000697205.1	c.1195G>A	p.Ala399Thr	missense_variant	Exon 11 of 17			ENSP00000513185.1

Frequencies

GnomAD3 genomes AF: 0.0114 AC: 1735 AN: 152172 Hom.: 13 Cov.: 32

Gnomad AFR AF: 0.00331

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.0191

Gnomad ASJ AF: 0.0190

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00373

Gnomad FIN AF: 0.00631

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0160

Gnomad OTH AF: 0.0187

GnomAD2 exomes AF: 0.0115 AC: 2870 AN: 249496 AF XY: 0.0115

Gnomad AFR exome AF: 0.00207

Gnomad AMR exome AF: 0.0152

Gnomad ASJ exome AF: 0.0221

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00761

Gnomad NFE exome AF: 0.0152

Gnomad OTH exome AF: 0.0150

GnomAD4 exome AF: 0.0127 AC: 18621 AN: 1461882 Hom.: 148 Cov.: 32 AF XY: 0.0126 AC XY: 9149 AN XY: 727244

Gnomad4 AFR exome AF: 0.00179 AC: 60 AN: 33478

Gnomad4 AMR exome AF: 0.0153 AC: 685 AN: 44724

Gnomad4 ASJ exome AF: 0.0222 AC: 579 AN: 26136

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 39700

Gnomad4 SAS exome AF: 0.00349 AC: 301 AN: 86258

Gnomad4 FIN exome AF: 0.00889 AC: 475 AN: 53418

Gnomad4 NFE exome AF: 0.0141 AC: 15675 AN: 1112004

Gnomad4 Remaining exome AF: 0.0133 AC: 806 AN: 60396

GnomAD4 genome AF: 0.0114 AC: 1734 AN: 152290 Hom.: 13 Cov.: 32 AF XY: 0.0112 AC XY: 831 AN XY: 74474

Gnomad4 AFR AF: 0.00330 AC: 0.00329723 AN: 0.00329723

Gnomad4 AMR AF: 0.0191 AC: 0.0190775 AN: 0.0190775

Gnomad4 ASJ AF: 0.0190 AC: 0.0190311 AN: 0.0190311

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.00373 AC: 0.00372825 AN: 0.00372825

Gnomad4 FIN AF: 0.00631 AC: 0.00631004 AN: 0.00631004

Gnomad4 NFE AF: 0.0160 AC: 0.0159962 AN: 0.0159962

Gnomad4 OTH AF: 0.0185 AC: 0.0184834 AN: 0.0184834

Alfa AF: 0.0142 Hom.: 56

Bravo AF: 0.0121

TwinsUK AF: 0.0154 AC: 57

ALSPAC AF: 0.0114 AC: 44

ESP6500AA AF: 0.00201 AC: 8

ESP6500EA AF: 0.0144 AC: 120

ExAC AF: 0.0108 AC: 1307

Asia WGS AF: 0.00318 AC: 11 AN: 3478

EpiCase AF: 0.0177

EpiControl AF: 0.0161

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	T
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.97	D
MetaRNN	Benign	0.0065	T
MetaSVM	Benign	-0.70	T
MutationAssessor	Uncertain	2.4	M
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.18
Sift	Benign	0.054	T
Sift4G	Benign	0.17	T
Polyphen		0.60	P
Vest4		0.68
MPC		0.12
ClinPred		0.013	T
GERP RS		5.6
Varity_R		0.14
gMVP		0.56
Mutation Taster		=74/26	polymorphism

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

Publications

LitVar

Other links and lift over

dbSNP: rs56031549; hg19: chr2-168931636;