chr8-66840043-A-G

Variant names:

• chr8-66840043-A-G
• rs193920898
• NM_001033578.3:c.782A>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The ENST00000521198.7(SGK3):​c.782A>G​(p.His261Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,784 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: SGK3 ENST00000521198.7 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 3.47
• Publications: 1 publications found

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: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]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.14752358).
• BS2: High AC in GnomAdExome4 at 9 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000521198.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGK3	NM_001033578.3	MANE Select	c.782A>G	p.His261Arg	missense	Exon 11 of 17	NP_001028750.1
	C8orf44-SGK3	NM_001204173.2		c.782A>G	p.His261Arg	missense	Exon 13 of 19	NP_001191102.1
	SGK3	NM_013257.5		c.782A>G	p.His261Arg	missense	Exon 11 of 17	NP_037389.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGK3	ENST00000521198.7	TSL:1 MANE Select	c.782A>G	p.His261Arg	missense	Exon 11 of 17	ENSP00000430463.1
	SGK3	ENST00000345714.8	TSL:1	c.782A>G	p.His261Arg	missense	Exon 10 of 16	ENSP00000331816.5
	SGK3	ENST00000396596.2	TSL:1	c.782A>G	p.His261Arg	missense	Exon 11 of 17	ENSP00000379842.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD2 exomes AF: 0.0000199 AC: 5 AN: 251424 AF XY: 0.0000221

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS 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: 0.00000616 AC: 9 AN: 1461784 Hom.: 0 Cov.: 32 AF XY: 0.00000963 AC XY: 7 AN XY: 727180

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.000104 AC: 9 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111958

Other (OTH) AF: 0.00 AC: 0 AN: 60386

GnomAD4 genome Cov.: 30

ExAC AF: 0.0000247 AC: 3

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	Prostate cancer (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	21
DANN	Benign	0.78
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.52
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	-0.040	N
PhyloP100		3.5
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-0.60	N
REVEL	Benign	0.088
Sift	Benign	0.031	D
Sift4G	Benign	0.37	T
Polyphen		0.0090	B
Vest4		0.40
MutPred		0.47		Gain of solvent accessibility (P = 0.0374)
MVP		0.21
MPC		0.62
ClinPred		0.11	T
GERP RS		2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.15
gMVP		0.58
Mutation Taster		=55/45	polymorphism

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

Other links and lift over

dbSNP: rs193920898; hg19: chr8-67752278; COSMIC: COSV61895707; COSMIC: COSV61895707;