5-172052937-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_005990.4(STK10):c.2758C>T(p.Arg920Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000198 in 1,613,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000053 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000016 ( 0 hom. )
Consequence
STK10
NM_005990.4 missense
NM_005990.4 missense
Scores
10
8
1
Clinical Significance
Conservation
PhyloP100: 4.08
Genes affected
STK10 (HGNC:11388): (serine/threonine kinase 10) This gene encodes a member of the Ste20 family of serine/threonine protein kinases, and is similar to several known polo-like kinase kinases. The protein can associate with and phosphorylate polo-like kinase 1, and overexpression of a kinase-dead version of the protein interferes with normal cell cycle progression. The kinase can also negatively regulate interleukin 2 expression in T-cells via the mitogen activated protein kinase kinase 1 pathway. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.869
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
STK10 | NM_005990.4 | c.2758C>T | p.Arg920Cys | missense_variant | 18/19 | ENST00000176763.10 | |
STK10 | XM_047417627.1 | c.2368C>T | p.Arg790Cys | missense_variant | 15/16 | ||
STK10 | XM_047417628.1 | c.2209C>T | p.Arg737Cys | missense_variant | 17/18 | ||
STK10 | XM_047417629.1 | c.2074C>T | p.Arg692Cys | missense_variant | 16/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
STK10 | ENST00000176763.10 | c.2758C>T | p.Arg920Cys | missense_variant | 18/19 | 1 | NM_005990.4 | P1 | |
STK10 | ENST00000520476.1 | c.577C>T | p.Arg193Cys | missense_variant | 5/7 | 2 | |||
STK10 | ENST00000517360.1 | n.264C>T | non_coding_transcript_exon_variant | 1/2 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000526 AC: 8AN: 152188Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000359 AC: 9AN: 251006Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135702
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GnomAD4 exome AF: 0.0000164 AC: 24AN: 1461652Hom.: 0 Cov.: 30 AF XY: 0.0000165 AC XY: 12AN XY: 727102
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GnomAD4 genome AF: 0.0000526 AC: 8AN: 152188Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74332
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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 | May 11, 2022 | The c.2758C>T (p.R920C) alteration is located in exon 18 (coding exon 18) of the STK10 gene. This alteration results from a C to T substitution at nucleotide position 2758, causing the arginine (R) at amino acid position 920 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Uncertain
D
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D
REVEL
Pathogenic
Sift
Pathogenic
D
Sift4G
Pathogenic
D
Polyphen
D
Vest4
MutPred
Gain of catalytic residue at P919 (P = 0.0082);
MVP
MPC
ClinPred
D
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