chr8-66813885-G-A
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_001033578.3(SGK3):c.286G>A(p.Glu96Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000686 in 1,588,062 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000061 ( 0 hom. )
Consequence
SGK3
NM_001033578.3 missense
NM_001033578.3 missense
Scores
2
4
11
Clinical Significance
Conservation
PhyloP100: 7.19
Genes affected
SGK3 (HGNC:10812): (serum/glucocorticoid regulated kinase family member 3) This gene is a member of the Ser/Thr protein kinase family and encodes a phosphoprotein with a PX (phox homology) domain. The protein phosphorylates several target proteins and has a role in neutral amino acid transport and activation of potassium and chloride channels. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [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=0.09361747).
BS2
High AC in GnomAd4 at 21 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SGK3 | NM_001033578.3 | c.286G>A | p.Glu96Lys | missense_variant | 5/17 | ENST00000521198.7 | |
C8orf44-SGK3 | NM_001204173.2 | c.286G>A | p.Glu96Lys | missense_variant | 7/19 | ||
SGK3 | NM_013257.5 | c.286G>A | p.Glu96Lys | missense_variant | 5/17 | ||
SGK3 | NM_170709.3 | c.286G>A | p.Glu96Lys | missense_variant | 5/16 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SGK3 | ENST00000521198.7 | c.286G>A | p.Glu96Lys | missense_variant | 5/17 | 1 | NM_001033578.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000138 AC: 21AN: 151942Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000128 AC: 30AN: 234836Hom.: 0 AF XY: 0.0000863 AC XY: 11AN XY: 127426
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GnomAD4 exome AF: 0.0000613 AC: 88AN: 1436120Hom.: 0 Cov.: 30 AF XY: 0.0000518 AC XY: 37AN XY: 713874
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GnomAD4 genome AF: 0.000138 AC: 21AN: 151942Hom.: 0 Cov.: 32 AF XY: 0.000162 AC XY: 12AN XY: 74228
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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 | Mar 29, 2022 | The c.286G>A (p.E96K) alteration is located in exon 5 (coding exon 4) of the SGK3 gene. This alteration results from a G to A substitution at nucleotide position 286, causing the glutamic acid (E) at amino acid position 96 to be replaced by a lysine (K). 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
Uncertain
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T;T;T;.;T;.;.;T;T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N;N;.;N;.;N;.;N;.
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;N;N;D;N;N;N;N;N;N
REVEL
Benign
Sift
Benign
T;T;T;D;T;T;T;T;T;D
Sift4G
Benign
T;T;T;D;T;T;T;T;T;T
Polyphen
D;D;D;.;D;.;D;.;D;.
Vest4
MVP
MPC
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