6-134172809-A-G

Variant names:

• chr6-134172809-A-G
• rs1743966
• NM_001143676.3:c.835-35T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 27 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001143676.3. 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
	SGK1	NM_001143676.3	MANE Select	c.835-35T>C		intron	N/A	NP_001137148.1
	SGK1	NM_001143677.2		c.634-35T>C		intron	N/A	NP_001137149.1
	SGK1	NM_001143678.2		c.592-35T>C		intron	N/A	NP_001137150.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGK1	ENST00000367858.10	TSL:1 MANE Select	c.835-35T>C		intron	N/A	ENSP00000356832.5
	SGK1	ENST00000528577.5	TSL:1	c.634-35T>C		intron	N/A	ENSP00000434450.1
	SGK1	ENST00000413996.7	TSL:1	c.592-35T>C		intron	N/A	ENSP00000396242.3

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

GnomAD2 exomes AF: 0.221 AC: 54321 AN: 245674 AF XY: 0.213

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 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

African (AFR) AF: 0.299 AC: 9184 AN: 30676

American (AMR) AF: 0.274 AC: 12025 AN: 43916

Ashkenazi Jewish (ASJ) AF: 0.285 AC: 7191 AN: 25242

East Asian (EAS) AF: 0.226 AC: 8809 AN: 38988

South Asian (SAS) AF: 0.129 AC: 10701 AN: 83226

European-Finnish (FIN) AF: 0.230 AC: 12258 AN: 53276

Middle Eastern (MID) AF: 0.208 AC: 1151 AN: 5528

European-Non Finnish (NFE) AF: 0.208 AC: 205640 AN: 987714

Other (OTH) AF: 0.220 AC: 12303 AN: 55814

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

African (AFR) AF: 0.297 AC: 12344 AN: 41502

American (AMR) AF: 0.254 AC: 3879 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.289 AC: 1004 AN: 3472

East Asian (EAS) AF: 0.239 AC: 1239 AN: 5176

South Asian (SAS) AF: 0.128 AC: 617 AN: 4828

European-Finnish (FIN) AF: 0.234 AC: 2480 AN: 10582

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.208 AC: 14171 AN: 67978

Other (OTH) AF: 0.245 AC: 517 AN: 2110

Alfa AF: 0.221 Hom.: 10014

Bravo AF: 0.247

Asia WGS AF: 0.199 AC: 694 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	9.7
DANN	Benign	0.62
PhyloP100		1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

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