8-66850901-C-A

Position:

• chr8-66850901-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001033578.3(SGK3):​c.1301C>A​(p.Pro434Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SGK3 NM_001033578.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.49

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 Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.82

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SGK3	NM_001033578.3	c.1301C>A	p.Pro434Gln	missense_variant	16/17	ENST00000521198.7
C8orf44-SGK3	NM_001204173.2	c.1301C>A	p.Pro434Gln	missense_variant	18/19
SGK3	NM_013257.5	c.1301C>A	p.Pro434Gln	missense_variant	16/17
SGK3	NM_170709.3	c.1205C>A	p.Pro402Gln	missense_variant	15/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SGK3	ENST00000521198.7	c.1301C>A	p.Pro434Gln	missense_variant	16/17	1	NM_001033578.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

Jun 07, 2023

The c.1301C>A (p.P434Q) alteration is located in exon 16 (coding exon 15) of the SGK3 gene. This alteration results from a C to A substitution at nucleotide position 1301, causing the proline (P) at amino acid position 434 to be replaced by a glutamine (Q). 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	0.94
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Pathogenic	30
DANN	Uncertain	0.99
DEOGEN2	Pathogenic	0.82	D;D;D;D;.;D
Eigen	Pathogenic	1.1
Eigen_PC	Pathogenic	0.97
FATHMM_MKL	Pathogenic	0.99	D
M_CAP	Benign	0.082	D
MetaRNN	Pathogenic	0.82	D;D;D;D;D;D
MetaSVM	Uncertain	0.60	D
MutationAssessor	Pathogenic	4.6	H;H;H;H;.;H
PrimateAI	Uncertain	0.68	T
PROVEAN	Pathogenic	-7.3	D;D;D;D;D;D
REVEL	Uncertain	0.50
Sift	Uncertain	0.0010	D;D;D;D;D;D
Sift4G	Pathogenic	0.0010	D;D;D;D;D;D
Polyphen		1.0	D;D;D;D;D;D
Vest4		0.82
MutPred		0.61		Loss of catalytic residue at P433 (P = 0.0219);Loss of catalytic residue at P433 (P = 0.0219);Loss of catalytic residue at P433 (P = 0.0219);Loss of catalytic residue at P433 (P = 0.0219);.;Loss of catalytic residue at P433 (P = 0.0219);
MVP		0.79
MPC		0.38
ClinPred		1.0	D
GERP RS		5.4
Varity_R		0.76
gMVP		0.92

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-67763136;