chr8-98526777-T-A
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_006281.4(STK3):c.1282A>T(p.Asn428Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000442 in 1,583,932 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000042 ( 0 hom. )
Consequence
STK3
NM_006281.4 missense
NM_006281.4 missense
Scores
7
8
Clinical Significance
Conservation
PhyloP100: 5.77
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 Likely_benign. Variant got -4 ACMG points.
BS2
High AC in GnomAdExome4 at 6 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
STK3 | NM_006281.4 | c.1282A>T | p.Asn428Tyr | missense_variant | 10/11 | ENST00000419617.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
STK3 | ENST00000419617.7 | c.1282A>T | p.Asn428Tyr | missense_variant | 10/11 | 1 | NM_006281.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152164Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000422 AC: 1AN: 236826Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 128236
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GnomAD4 exome AF: 0.00000419 AC: 6AN: 1431768Hom.: 0 Cov.: 30 AF XY: 0.00000704 AC XY: 5AN XY: 710444
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152164Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74328
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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 | Oct 17, 2023 | The c.1282A>T (p.N428Y) alteration is located in exon 10 (coding exon 10) of the STK3 gene. This alteration results from a A to T substitution at nucleotide position 1282, causing the asparagine (N) at amino acid position 428 to be replaced by a tyrosine (Y). 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
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
T
MetaRNN
Uncertain
D;D;D
MetaSVM
Benign
T
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
Sift4G
Benign
T;T;T
Polyphen
0.0010
.;B;.
Vest4
MutPred
0.33
.;Loss of disorder (P = 0.0163);.;
MVP
MPC
0.085
ClinPred
T
GERP RS
Varity_R
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