Variant 8-66813885-G-A details in Genebe, Genetics Data Aggregator

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

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.19

Variant links:

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]

SGK3 links:

C8orf44-SGK3 (HGNC:):

C8orf44-SGK3 links:

Genome browser will be placed here

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
SGK3	NM_001033578.3 linkuse as main transcript	c.286G>A	p.Glu96Lys	missense_variant	5/17	ENST00000521198.7
C8orf44-SGK3	NM_001204173.2 linkuse as main transcript	c.286G>A	p.Glu96Lys	missense_variant	7/19
SGK3	NM_013257.5 linkuse as main transcript	c.286G>A	p.Glu96Lys	missense_variant	5/17
SGK3	NM_170709.3 linkuse as main transcript	c.286G>A	p.Glu96Lys	missense_variant	5/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SGK3	ENST00000521198.7 linkuse as main transcript	c.286G>A	p.Glu96Lys	missense_variant	5/17	1	NM_001033578.3	P1	Q96BR1-1

Frequencies

GnomAD3 genomes

AF:

0.000138

AC:

AN:

151942

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000854

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000128

AC:

AN:

234836

Hom.:

AF XY:

0.0000863

AC XY:

AN XY:

127426

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000168

Gnomad ASJ exome

AF:

0.00234

Gnomad EAS exome

AF:

0.0000595

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000918

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000613

AC:

AN:

1436120

Hom.:

Cov.:

AF XY:

0.0000518

AC XY:

AN XY:

713874

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000122

Gnomad4 ASJ exome

AF:

0.00230

Gnomad4 EAS exome

AF:

0.0000263

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000100

Gnomad4 OTH exome

AF:

0.000203

GnomAD4 genome

AF:

0.000138

AC:

AN:

151942

Hom.:

Cov.:

AF XY:

0.000162

AC XY:

AN XY:

74228

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000854

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000248

Hom.:

Bravo

AF:

0.000121

ExAC

AF:

0.000124

AC:

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: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.34

BayesDel_addAF

Benign

-0.033

BayesDel_noAF

Uncertain

-0.020

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.32

T;T;T;.;T;.;.;T;T;T

Eigen

Uncertain

0.60

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Uncertain

0.96

M_CAP

Benign

0.014

MetaRNN

Benign

0.094

T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.71

N;N;N;.;N;.;N;.;N;.

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-2.1

N;N;N;D;N;N;N;N;N;N

REVEL

Benign

0.24

Sift

Benign

0.088

T;T;T;D;T;T;T;T;T;D

Sift4G

Benign

0.22

T;T;T;D;T;T;T;T;T;T

Polyphen

0.99

D;D;D;.;D;.;D;.;D;.

Vest4

0.59

MVP

0.53

MPC

0.80

ClinPred

0.22

GERP RS

5.5

Varity_R

0.65

gMVP

0.52

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over