8-66804396-A-G

Position:

• chr8-66804396-A-G

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4 BS2

The NM_001033578.3(SGK3):​c.202A>G​(p.Met68Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000685 in 1,459,070 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000069 (0 hom.)
• Consequence: SGK3 NM_001033578.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.44

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 -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.29267102).
• BS2: High AC in GnomAdExome4 at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SGK3	NM_001033578.3	c.202A>G	p.Met68Val	missense_variant	4/17	ENST00000521198.7
C8orf44-SGK3	NM_001204173.2	c.202A>G	p.Met68Val	missense_variant	6/19
SGK3	NM_013257.5	c.202A>G	p.Met68Val	missense_variant	4/17
SGK3	NM_170709.3	c.202A>G	p.Met68Val	missense_variant	4/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SGK3	ENST00000521198.7	c.202A>G	p.Met68Val	missense_variant	4/17	1	NM_001033578.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000685 AC: 10 AN: 1459070 Hom.: 0 Cov.: 30 AF XY: 0.00000965 AC XY: 7 AN XY: 725728

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000897

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000505

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000360

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 08, 2024

The c.202A>G (p.M68V) alteration is located in exon 4 (coding exon 3) of the SGK3 gene. This alteration results from a A to G substitution at nucleotide position 202, causing the methionine (M) at amino acid position 68 to be replaced by a valine (V). 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	0.067
BayesDel_addAF	Benign	-0.078	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.15	T;T;T;.;T;.;.;T;T;T
Eigen	Benign	-0.25
Eigen_PC	Benign	0.012
FATHMM_MKL	Uncertain	0.90	D
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.18	T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.54	N;N;N;.;N;.;N;.;N;.
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-0.41	N;N;N;N;N;N;N;N;N;N
REVEL	Benign	0.12
Sift	Benign	0.32	T;T;T;D;T;T;T;T;T;D
Sift4G	Benign	0.29	T;T;T;T;T;T;T;T;T;D
Polyphen		0.0010	B;B;B;.;B;.;B;.;B;.
Vest4		0.42
MutPred		0.50		Gain of catalytic residue at Q64 (P = 0.1037);Gain of catalytic residue at Q64 (P = 0.1037);Gain of catalytic residue at Q64 (P = 0.1037);.;Gain of catalytic residue at Q64 (P = 0.1037);Gain of catalytic residue at Q64 (P = 0.1037);Gain of catalytic residue at Q64 (P = 0.1037);Gain of catalytic residue at Q64 (P = 0.1037);Gain of catalytic residue at Q64 (P = 0.1037);.;
MVP		0.25
MPC		0.41
ClinPred		0.78	D
GERP RS		5.4
Varity_R		0.49
gMVP		0.36

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: rs1808070515; hg19: chr8-67716631;