8-66840018-C-A

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001033578.3(SGK3):c.757C>A(p.Gln253Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,611,716 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SGK3
NM_001033578.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.84

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:48354): (C8orf44-SGK3 readthrough) This locus represents naturally occurring read-through transcription between the neighboring putative uncharacterized protein C8orf44 (GeneID 56260) and serine/threonine-protein kinase Sgk3 (GeneID 23678) genes on chromosome 8. The read-through transcript produces a protein that shares sequence identity with the downstream gene product. [provided by RefSeq, Feb 2011]

C8orf44-SGK3 links:

Genome browser will be placed here

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 rank	MANE	Protein	UniProt
SGK3	NM_001033578.3 link	c.757C>A	p.Gln253Lys	missense_variant	Exon 11 of 17	ENST00000521198.7	NP_001028750.1	Q96BR1-1A0A024R807Q5H9Q5
C8orf44-SGK3	NM_001204173.2 link	c.757C>A	p.Gln253Lys	missense_variant	Exon 13 of 19		NP_001191102.1	Q96BR1-1A0A024R807
SGK3	NM_013257.5 link	c.757C>A	p.Gln253Lys	missense_variant	Exon 11 of 17		NP_037389.4	Q96BR1-1A0A024R807Q53EW6Q5H9Q5
SGK3	NM_170709.3 link	c.757C>A	p.Gln253Lys	missense_variant	Exon 11 of 16		NP_733827.2	Q96BR1-2Q53EW6Q5H9Q5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SGK3	ENST00000521198.7 link	c.757C>A	p.Gln253Lys	missense_variant	Exon 11 of 17	1	NM_001033578.3	ENSP00000430463.1		Q96BR1-1
C8orf44-SGK3	ENST00000519289.1 link	c.757C>A	p.Gln253Lys	missense_variant	Exon 13 of 19	2		ENSP00000429022.1

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151994

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.00000398

AC:

AN:

251104

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135696

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000545

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1459722

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726154

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

151994

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74242

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

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:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 14, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.757C>A (p.Q253K) alteration is located in exon 11 (coding exon 10) of the SGK3 gene. This alteration results from a C to A substitution at nucleotide position 757, causing the glutamine (Q) at amino acid position 253 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

Pathogenic

0.90

BayesDel_addAF

Benign

-0.031

BayesDel_noAF

Benign

-0.11

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.35

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

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.93

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

M_CAP

Benign

0.039

MetaRNN

Uncertain

0.69

D;D;D;D;D;D;D

MetaSVM

Benign

-0.44

MutationAssessor

Benign

0.36

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

PrimateAI

Pathogenic

0.84

PROVEAN

Uncertain

-3.9

D;D;D;D;D;D;D

REVEL

Uncertain

0.42

Sift

Benign

0.10

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

Sift4G

Benign

0.11

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

Polyphen

1.0

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

Vest4

0.91

MutPred

0.64

Gain of methylation at Q253 (P = 0.0285);Gain of methylation at Q253 (P = 0.0285);Gain of methylation at Q253 (P = 0.0285);Gain of methylation at Q253 (P = 0.0285);Gain of methylation at Q253 (P = 0.0285);Gain of methylation at Q253 (P = 0.0285);.;

MVP

0.69

MPC

0.51

ClinPred

0.73

GERP RS

5.3

Varity_R

0.81

gMVP

0.64

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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