rs193920898

chr8-66840043-A-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001033578.3(SGK3):c.782A>G(p.His261Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,784 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: SGK3 NM_001033578.3 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 3.47

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]

C8orf44-SGK3 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.14752358).
• BS2: High AC in GnomAdExome at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SGK3	NM_001033578.3	c.782A>G	p.His261Arg	missense_variant	11/17	ENST00000521198.7
C8orf44-SGK3	NM_001204173.2	c.782A>G	p.His261Arg	missense_variant	13/19
SGK3	NM_013257.5	c.782A>G	p.His261Arg	missense_variant	11/17
SGK3	NM_170709.3	c.782A>G	p.His261Arg	missense_variant	11/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SGK3	ENST00000521198.7	c.782A>G	p.His261Arg	missense_variant	11/17	1	NM_001033578.3	P1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD3 exomes AF: 0.0000199 AC: 5 AN: 251424 Hom.: 0 AF XY: 0.0000221 AC XY: 3 AN XY: 135882

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000616 AC: 9 AN: 1461784 Hom.: 0 Cov.: 32 AF XY: 0.00000963 AC XY: 7 AN XY: 727180

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000104

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

ExAC AF: 0.0000247 AC: 3

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Malignant tumor of prostate Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

Science for Life laboratory, Karolinska Institutet

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.36
Cadd	Benign	21
Dann	Benign	0.78
DEOGEN2	Benign	0.16	T;T;T;T;.;T;T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.52
FATHMM_MKL	Uncertain	0.90	D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.15	T;T;T;T;T;T;T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	-0.040	N;N;N;N;N;N;.
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-0.60	N;N;N;N;N;N;N
REVEL	Benign	0.088
Sift	Benign	0.031	D;D;D;D;D;D;D
Sift4G	Benign	0.37	T;T;T;T;T;T;T
Polyphen		0.0090	B;B;B;B;B;B;.
Vest4		0.40
MutPred		0.47		Gain of solvent accessibility (P = 0.0374);Gain of solvent accessibility (P = 0.0374);Gain of solvent accessibility (P = 0.0374);Gain of solvent accessibility (P = 0.0374);Gain of solvent accessibility (P = 0.0374);Gain of solvent accessibility (P = 0.0374);.;
MVP		0.21
MPC		0.62
ClinPred		0.11	T
GERP RS		2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.15
gMVP		0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs193920898; hg19: chr8-67752278; COSMIC: COSV61895707; COSMIC: COSV61895707;