2-168163844-C-T
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_013233.3(STK39):c.467G>A(p.Arg156Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000161 in 1,613,808 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000099 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000075 ( 0 hom. )
Consequence
STK39
NM_013233.3 missense
NM_013233.3 missense
Scores
4
15
Clinical Significance
Conservation
PhyloP100: 3.79
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 Likely_benign. Variant got -6 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.117610395).
BS2
High AC in GnomAd4 at 15 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
STK39 | NM_013233.3 | c.467G>A | p.Arg156Gln | missense_variant | 4/18 | ENST00000355999.5 | NP_037365.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
STK39 | ENST00000355999.5 | c.467G>A | p.Arg156Gln | missense_variant | 4/18 | 1 | NM_013233.3 | ENSP00000348278.4 | ||
STK39 | ENST00000697205.1 | c.467G>A | p.Arg156Gln | missense_variant | 4/17 | ENSP00000513185.1 |
Frequencies
GnomAD3 genomes AF: 0.0000986 AC: 15AN: 152172Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000241 AC: 6AN: 248982Hom.: 0 AF XY: 0.00000740 AC XY: 1AN XY: 135082
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GnomAD4 exome AF: 0.00000753 AC: 11AN: 1461636Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5AN XY: 727120
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GnomAD4 genome AF: 0.0000986 AC: 15AN: 152172Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 8AN XY: 74336
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 22, 2023 | The c.467G>A (p.R156Q) alteration is located in exon 4 (coding exon 4) of the STK39 gene. This alteration results from a G to A substitution at nucleotide position 467, causing the arginine (R) at amino acid position 156 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
B
Vest4
MVP
MPC
ClinPred
T
GERP RS
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at