rs1009840

Positions:

• chr6-134225547-G-A

Variant summary

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

The NM_001143676.3(SGK1):​c.286-18116C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.543 in 151,712 control chromosomes in the GnomAD database, including 26,502 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 0.54 (26502 hom., cov: 29)
• Consequence: SGK1 NM_001143676.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.19

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.788 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SGK1	NM_001143676.3	c.286-18116C>T		intron_variant		ENST00000367858.10	NP_001137148.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SGK1	ENST00000367858.10	c.286-18116C>T		intron_variant		1	NM_001143676.3	ENSP00000356832

Frequencies

GnomAD3 genomes AF: 0.543 AC: 82385 AN: 151596 Hom.: 26500 Cov.: 29

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.629

Gnomad AMR AF: 0.555

Gnomad ASJ AF: 0.737

Gnomad EAS AF: 0.696

Gnomad SAS AF: 0.808

Gnomad FIN AF: 0.755

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.686

Gnomad OTH AF: 0.562

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

GnomAD4 genome AF: 0.543 AC: 82392 AN: 151712 Hom.: 26502 Cov.: 29 AF XY: 0.554 AC XY: 41017 AN XY: 74094

Gnomad4 AFR AF: 0.181

Gnomad4 AMR AF: 0.554

Gnomad4 ASJ AF: 0.737

Gnomad4 EAS AF: 0.696

Gnomad4 SAS AF: 0.809

Gnomad4 FIN AF: 0.755

Gnomad4 NFE AF: 0.686

Gnomad4 OTH AF: 0.565

Alfa AF: 0.651 Hom.: 19353

Bravo AF: 0.507

Asia WGS AF: 0.675 AC: 2349 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	4.8
DANN	Benign	0.81

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1009840; hg19: chr6-134546685; COSMIC: COSV63278988;