6-134209559-A-G

Variant names:

• chr6-134209559-A-G
• rs9493857
• NM_001143676.3:c.286-2128T>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.286-2128T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.632 in 152,208 control chromosomes in the GnomAD database, including 36,230 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 0.63 (36230 hom., cov: 33)
• Consequence: SGK1 NM_001143676.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.150
• Publications: 9 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.87 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SGK1	NM_001143676.3	c.286-2128T>C		intron_variant	Intron 2 of 13	ENST00000367858.10	NP_001137148.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SGK1	ENST00000367858.10	c.286-2128T>C		intron_variant	Intron 2 of 13	1	NM_001143676.3	ENSP00000356832.5

Frequencies

GnomAD3 genomes AF: 0.632 AC: 96158 AN: 152090 Hom.: 36230 Cov.: 33

Gnomad AFR AF: 0.200

Gnomad AMI AF: 0.836

Gnomad AMR AF: 0.629

Gnomad ASJ AF: 0.826

Gnomad EAS AF: 0.726

Gnomad SAS AF: 0.891

Gnomad FIN AF: 0.866

Gnomad MID AF: 0.718

Gnomad NFE AF: 0.820

Gnomad OTH AF: 0.646

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.632 AC: 96159 AN: 152208 Hom.: 36230 Cov.: 33 AF XY: 0.641 AC XY: 47677 AN XY: 74422

African (AFR) AF: 0.200 AC: 8312 AN: 41520

American (AMR) AF: 0.628 AC: 9597 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.826 AC: 2869 AN: 3472

East Asian (EAS) AF: 0.726 AC: 3763 AN: 5186

South Asian (SAS) AF: 0.892 AC: 4305 AN: 4826

European-Finnish (FIN) AF: 0.866 AC: 9178 AN: 10600

Middle Eastern (MID) AF: 0.718 AC: 211 AN: 294

European-Non Finnish (NFE) AF: 0.820 AC: 55795 AN: 68020

Other (OTH) AF: 0.649 AC: 1370 AN: 2112

Alfa AF: 0.749 Hom.: 52933

Bravo AF: 0.590

Asia WGS AF: 0.736 AC: 2561 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.0
DANN	Benign	0.66
PhyloP100		-0.15
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs9493857; hg19: chr6-134530697;