8-66847233-A-G
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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):āc.1115A>Gā(p.Asn372Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000682 in 1,613,596 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000020 ( 0 hom., cov: 32)
Exomes š: 0.0000055 ( 1 hom. )
Consequence
SGK3
NM_001033578.3 missense
NM_001033578.3 missense
Scores
1
2
14
Clinical Significance
Conservation
PhyloP100: 9.28
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=0.16014957).
BS2
High AC in GnomAdExome4 at 8 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SGK3 | NM_001033578.3 | c.1115A>G | p.Asn372Ser | missense_variant | 15/17 | ENST00000521198.7 | |
C8orf44-SGK3 | NM_001204173.2 | c.1115A>G | p.Asn372Ser | missense_variant | 17/19 | ||
SGK3 | NM_013257.5 | c.1115A>G | p.Asn372Ser | missense_variant | 15/17 | ||
SGK3 | NM_170709.3 | c.1019A>G | p.Asn340Ser | missense_variant | 14/16 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SGK3 | ENST00000521198.7 | c.1115A>G | p.Asn372Ser | missense_variant | 15/17 | 1 | NM_001033578.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 151990Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251134Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135720
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GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461606Hom.: 1 Cov.: 34 AF XY: 0.00000550 AC XY: 4AN XY: 727068
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 151990Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74248
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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 | Jun 26, 2023 | The c.1115A>G (p.N372S) alteration is located in exon 15 (coding exon 14) of the SGK3 gene. This alteration results from a A to G substitution at nucleotide position 1115, causing the asparagine (N) at amino acid position 372 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
Benign
DEOGEN2
Benign
T;T;T;T;.;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N;N;N;.;N
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D;D;D;D
REVEL
Benign
Sift
Benign
D;D;D;D;D;D
Sift4G
Benign
T;T;T;T;T;T
Polyphen
B;B;B;B;B;B
Vest4
MutPred
Gain of disorder (P = 0.0914);Gain of disorder (P = 0.0914);Gain of disorder (P = 0.0914);Gain of disorder (P = 0.0914);.;Gain of disorder (P = 0.0914);
MVP
MPC
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T
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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