chr8-66835944-A-G
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001033578.3(SGK3):āc.611A>Gā(p.Gln204Arg) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,552 control chromosomes in the GnomAD database, with no homozygous occurrence. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: not found (cov: 32)
Exomes š: 0.0000014 ( 0 hom. )
Consequence
SGK3
NM_001033578.3 missense, splice_region
NM_001033578.3 missense, splice_region
Scores
2
8
7
Splicing: ADA: 0.8674
2
Clinical Significance
Conservation
PhyloP100: 9.32
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 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 |
---|---|---|---|---|---|---|---|
SGK3 | NM_001033578.3 | c.611A>G | p.Gln204Arg | missense_variant, splice_region_variant | 10/17 | ENST00000521198.7 | |
C8orf44-SGK3 | NM_001204173.2 | c.611A>G | p.Gln204Arg | missense_variant, splice_region_variant | 12/19 | ||
SGK3 | NM_013257.5 | c.611A>G | p.Gln204Arg | missense_variant, splice_region_variant | 10/17 | ||
SGK3 | NM_170709.3 | c.611A>G | p.Gln204Arg | missense_variant, splice_region_variant | 10/16 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SGK3 | ENST00000521198.7 | c.611A>G | p.Gln204Arg | missense_variant, splice_region_variant | 10/17 | 1 | NM_001033578.3 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250688Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135542
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GnomAD4 exome AF: 0.00000137 AC: 2AN: 1460552Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 726594
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GnomAD4 genome Cov.: 32
GnomAD4 genome
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32
ExAC
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1
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 | Dec 15, 2021 | The c.611A>G (p.Q204R) alteration is located in exon 10 (coding exon 9) of the SGK3 gene. This alteration results from a A to G substitution at nucleotide position 611, causing the glutamine (Q) at amino acid position 204 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T;T;T;.;T;T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D;D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Benign
N;N;N;N;N;N;.;.
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;N;N;N;N;N;N;N
REVEL
Uncertain
Sift
Benign
T;T;T;T;T;T;T;T
Sift4G
Benign
T;T;T;T;T;T;T;T
Polyphen
B;B;B;B;B;B;.;.
Vest4
MutPred
Gain of MoRF binding (P = 0.0168);Gain of MoRF binding (P = 0.0168);Gain of MoRF binding (P = 0.0168);Gain of MoRF binding (P = 0.0168);Gain of MoRF binding (P = 0.0168);Gain of MoRF binding (P = 0.0168);.;.;
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at