rs1057293

Positions:

• chr6-134172259-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001143676.3(SGK1):​c.1005C>T​(p.Asp335=) variant causes a synonymous change. The variant allele was found at a frequency of 0.106 in 1,613,382 control chromosomes in the GnomAD database, including 9,780 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.11 (956 hom., cov: 33)
  • Exomes 𝑓: 0.11 (8824 hom.)
• Consequence: SGK1 NM_001143676.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.00

Genes affected

SGK1 (HGNC:10810): (serum/glucocorticoid regulated kinase 1) This gene encodes a serine/threonine protein kinase that plays an important role in cellular stress response. This kinase activates certain potassium, sodium, and chloride channels, suggesting an involvement in the regulation of processes such as cell survival, neuronal excitability, and renal sodium excretion. High levels of expression of this gene may contribute to conditions such as hypertension and diabetic nephropathy. Several alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Jan 2009]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SGK1	NM_001143676.3	c.1005C>T	p.Asp335=	synonymous_variant	10/14	ENST00000367858.10	NP_001137148.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SGK1	ENST00000367858.10	c.1005C>T	p.Asp335=	synonymous_variant	10/14	1	NM_001143676.3	ENSP00000356832

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16580 AN: 152096 Hom.: 952 Cov.: 33

Gnomad AFR AF: 0.0948

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.196

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0995

Gnomad OTH AF: 0.104

GnomAD3 exomes AF: 0.124 AC: 31078 AN: 251264 Hom.: 2296 AF XY: 0.120 AC XY: 16274 AN XY: 135810

Gnomad AFR exome AF: 0.0949

Gnomad AMR exome AF: 0.206

Gnomad ASJ exome AF: 0.129

Gnomad EAS exome AF: 0.205

Gnomad SAS exome AF: 0.0995

Gnomad FIN exome AF: 0.126

Gnomad NFE exome AF: 0.0958

Gnomad OTH exome AF: 0.114

GnomAD4 exome AF: 0.106 AC: 154181 AN: 1461168 Hom.: 8824 Cov.: 31 AF XY: 0.105 AC XY: 76261 AN XY: 726918

Gnomad4 AFR exome AF: 0.0914

Gnomad4 AMR exome AF: 0.199

Gnomad4 ASJ exome AF: 0.125

Gnomad4 EAS exome AF: 0.187

Gnomad4 SAS exome AF: 0.102

Gnomad4 FIN exome AF: 0.125

Gnomad4 NFE exome AF: 0.0979

Gnomad4 OTH exome AF: 0.113

GnomAD4 genome AF: 0.109 AC: 16600 AN: 152214 Hom.: 956 Cov.: 33 AF XY: 0.111 AC XY: 8292 AN XY: 74410

Gnomad4 AFR AF: 0.0948

Gnomad4 AMR AF: 0.155

Gnomad4 ASJ AF: 0.128

Gnomad4 EAS AF: 0.196

Gnomad4 SAS AF: 0.100

Gnomad4 FIN AF: 0.123

Gnomad4 NFE AF: 0.0995

Gnomad4 OTH AF: 0.103

Alfa AF: 0.102 Hom.: 1150

Bravo AF: 0.111

Asia WGS AF: 0.149 AC: 517 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	13
DANN	Benign	0.91
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs1057293; hg19: chr6-134493397; COSMIC: COSV52804340; COSMIC: COSV52804340;