chr2-168075210-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2

The NM_013233.3(STK39):​c.1111A>G​(p.Ser371Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,776 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

STK39
NM_013233.3 missense

Scores

6
11
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.02
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM1
In a modified_residue Phosphoserine (size 0) in uniprot entity STK39_HUMAN
PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
STK39NM_013233.3 linkc.1111A>G p.Ser371Gly missense_variant Exon 11 of 18 ENST00000355999.5 NP_037365.2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
STK39ENST00000355999.5 linkc.1111A>G p.Ser371Gly missense_variant Exon 11 of 18 1 NM_013233.3 ENSP00000348278.4 Q9UEW8-1
STK39ENST00000487143.5 linkn.211A>G non_coding_transcript_exon_variant Exon 2 of 9 1
STK39ENST00000697205.1 linkc.1111A>G p.Ser371Gly missense_variant Exon 11 of 17 ENSP00000513185.1 A0A8V8TKT5

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461776
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
727192
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jul 27, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1111A>G (p.S371G) alteration is located in exon 11 (coding exon 11) of the STK39 gene. This alteration results from a A to G substitution at nucleotide position 1111, causing the serine (S) at amino acid position 371 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.89
BayesDel_addAF
Pathogenic
0.19
D
BayesDel_noAF
Uncertain
0.040
CADD
Pathogenic
29
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.71
D
Eigen
Pathogenic
0.68
Eigen_PC
Pathogenic
0.70
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Pathogenic
1.0
D
M_CAP
Benign
0.049
D
MetaRNN
Uncertain
0.65
D
MetaSVM
Uncertain
-0.018
T
MutationAssessor
Uncertain
2.6
M
PrimateAI
Uncertain
0.76
T
PROVEAN
Uncertain
-3.9
D
REVEL
Uncertain
0.51
Sift
Uncertain
0.016
D
Sift4G
Uncertain
0.019
D
Polyphen
0.99
D
Vest4
0.63
MutPred
0.21
Loss of glycosylation at S371 (P = 0.0172);
MVP
0.75
MPC
1.1
ClinPred
0.98
D
GERP RS
5.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.51
gMVP
0.38

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-168931720; API