chr6-134172809-A-G

Position:

• chr6-134172809-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001143676.3(SGK1):​c.835-35T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 1,476,506 control chromosomes in the GnomAD database, including 34,906 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 0.24 (4546 hom., cov: 32)
  • Exomes 𝑓: 0.21 (30360 hom.)
• Consequence: SGK1 NM_001143676.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.94

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]

SGK1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SGK1	NM_001143676.3	c.835-35T>C		intron_variant		ENST00000367858.10	NP_001137148.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SGK1	ENST00000367858.10	c.835-35T>C		intron_variant		1	NM_001143676.3	ENSP00000356832.5

Frequencies

GnomAD3 genomes AF: 0.239 AC: 36371 AN: 152008 Hom.: 4533 Cov.: 32

Gnomad AFR AF: 0.297

Gnomad AMI AF: 0.100

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.289

Gnomad EAS AF: 0.240

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.248

GnomAD3 exomes AF: 0.221 AC: 54321 AN: 245674 Hom.: 6244 AF XY: 0.213 AC XY: 28326 AN XY: 132838

Gnomad AFR exome AF: 0.299

Gnomad AMR exome AF: 0.276

Gnomad ASJ exome AF: 0.288

Gnomad EAS exome AF: 0.249

Gnomad SAS exome AF: 0.125

Gnomad FIN exome AF: 0.236

Gnomad NFE exome AF: 0.206

Gnomad OTH exome AF: 0.226

GnomAD4 exome AF: 0.211 AC: 279262 AN: 1324380 Hom.: 30360 Cov.: 19 AF XY: 0.208 AC XY: 138428 AN XY: 666460

Gnomad4 AFR exome AF: 0.299

Gnomad4 AMR exome AF: 0.274

Gnomad4 ASJ exome AF: 0.285

Gnomad4 EAS exome AF: 0.226

Gnomad4 SAS exome AF: 0.129

Gnomad4 FIN exome AF: 0.230

Gnomad4 NFE exome AF: 0.208

Gnomad4 OTH exome AF: 0.220

GnomAD4 genome AF: 0.239 AC: 36418 AN: 152126 Hom.: 4546 Cov.: 32 AF XY: 0.237 AC XY: 17655 AN XY: 74386

Gnomad4 AFR AF: 0.297

Gnomad4 AMR AF: 0.254

Gnomad4 ASJ AF: 0.289

Gnomad4 EAS AF: 0.239

Gnomad4 SAS AF: 0.128

Gnomad4 FIN AF: 0.234

Gnomad4 NFE AF: 0.208

Gnomad4 OTH AF: 0.245

Alfa AF: 0.220 Hom.: 6731

Bravo AF: 0.247

Asia WGS AF: 0.199 AC: 694 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	9.7
DANN	Benign	0.62
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs1743966; hg19: chr6-134493947; COSMIC: COSV52804386; COSMIC: COSV52804386;