chr8-98455849-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_006281.4(STK3):c.1469A>G(p.Asn490Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Consequence
STK3
NM_006281.4 missense
NM_006281.4 missense
Scores
2
8
5
Clinical Significance
Conservation
PhyloP100: 7.63
Genes affected
STK3 (HGNC:11406): (serine/threonine kinase 3) This gene encodes a serine/threonine protein kinase activated by proapoptotic molecules indicating the encoded protein functions as a growth suppressor. Cleavage of the protein product by caspase removes the inhibitory C-terminal portion. The N-terminal portion is transported to the nucleus where it homodimerizes to form the active kinase which promotes the condensation of chromatin during apoptosis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
STK3 | NM_006281.4 | c.1469A>G | p.Asn490Ser | missense_variant | 11/11 | ENST00000419617.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
STK3 | ENST00000419617.7 | c.1469A>G | p.Asn490Ser | missense_variant | 11/11 | 1 | NM_006281.4 | P1 | |
STK3 | ENST00000523601.5 | c.1553A>G | p.Asn518Ser | missense_variant | 13/13 | 2 | |||
STK3 | ENST00000617590.1 | c.1136A>G | p.Asn379Ser | missense_variant | 9/9 | 5 | |||
STK3 | ENST00000517832.1 | n.186-18641A>G | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome ? Cov.: 32
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
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 23, 2023 | The c.1469A>G (p.N490S) alteration is located in exon 11 (coding exon 11) of the STK3 gene. This alteration results from a A to G substitution at nucleotide position 1469, causing the asparagine (N) at amino acid position 490 to be replaced by a serine (S). 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
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D
M_CAP
Uncertain
D
MetaRNN
Uncertain
D;D;D
MetaSVM
Uncertain
D
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
Sift4G
Uncertain
D;D;D
Polyphen
0.98
.;D;.
Vest4
MutPred
0.22
.;Gain of phosphorylation at N490 (P = 0.0056);.;
MVP
MPC
0.33
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.