Variant 8-66847214-G-C 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.1096G>C(p.Val366Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000687 in 1,601,498 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 0.000040 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

SGK3
NM_001033578.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.35

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=0.18234652).

BS2

High AC in GnomAd4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SGK3	NM_001033578.3 linkuse as main transcript	c.1096G>C	p.Val366Leu	missense_variant	15/17	ENST00000521198.7
C8orf44-SGK3	NM_001204173.2 linkuse as main transcript	c.1096G>C	p.Val366Leu	missense_variant	17/19
SGK3	NM_013257.5 linkuse as main transcript	c.1096G>C	p.Val366Leu	missense_variant	15/17
SGK3	NM_170709.3 linkuse as main transcript	c.1000G>C	p.Val334Leu	missense_variant	14/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SGK3	ENST00000521198.7 linkuse as main transcript	c.1096G>C	p.Val366Leu	missense_variant	15/17	1	NM_001033578.3	P1	Q96BR1-1

Frequencies

GnomAD3 genomes

AF:

0.0000399

AC:

AN:

150432

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000398

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000818

AC:

AN:

244574

Hom.:

AF XY:

0.00000757

AC XY:

AN XY:

132150

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000304

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000167

GnomAD4 exome

AF:

0.00000345

AC:

AN:

1451066

Hom.:

Cov.:

AF XY:

0.00000277

AC XY:

AN XY:

721298

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000935

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

AF:

0.0000399

AC:

AN:

150432

Hom.:

Cov.:

AF XY:

0.0000546

AC XY:

AN XY:

73244

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000398

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000982

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 08, 2023

The c.1096G>C (p.V366L) alteration is located in exon 15 (coding exon 14) of the SGK3 gene. This alteration results from a G to C substitution at nucleotide position 1096, causing the valine (V) at amino acid position 366 to be replaced by a leucine (L). 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

Uncertain

0.56

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.35

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.22

T;T;T;T;.;T

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.027

FATHMM_MKL

Uncertain

0.96

M_CAP

Benign

0.012

MetaRNN

Benign

0.18

T;T;T;T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.025

N;N;N;N;.;N

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-1.3

N;N;N;N;N;N

REVEL

Benign

0.072

Sift

Benign

0.11

T;T;T;T;T;T

Sift4G

Benign

0.63

T;T;T;T;T;T

Polyphen

0.033

B;B;B;B;B;B

Vest4

0.29

MutPred

0.45

Loss of phosphorylation at Y370 (P = 0.2795);Loss of phosphorylation at Y370 (P = 0.2795);Loss of phosphorylation at Y370 (P = 0.2795);Loss of phosphorylation at Y370 (P = 0.2795);.;Loss of phosphorylation at Y370 (P = 0.2795);

MVP

0.36

MPC

0.50

ClinPred

0.40

GERP RS

4.6

Varity_R

0.24

gMVP

0.60

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