rs1009840

Variant names:

• chr6-134225547-G-A
• rs1009840
• NM_001143676.3:c.286-18116C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001143676.3(SGK1):​c.286-18116C>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
• Publications: 11 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=-0.59).
• 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 rank	MANE	Protein	UniProt
SGK1	NM_001143676.3	c.286-18116C>T		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.286-18116C>T		intron_variant	Intron 2 of 13	1	NM_001143676.3	ENSP00000356832.5

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

African (AFR) AF: 0.181 AC: 7483 AN: 41368

American (AMR) AF: 0.554 AC: 8441 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.737 AC: 2554 AN: 3464

East Asian (EAS) AF: 0.696 AC: 3574 AN: 5138

South Asian (SAS) AF: 0.809 AC: 3885 AN: 4800

European-Finnish (FIN) AF: 0.755 AC: 7916 AN: 10490

Middle Eastern (MID) AF: 0.643 AC: 189 AN: 294

European-Non Finnish (NFE) AF: 0.686 AC: 46588 AN: 67908

Other (OTH) AF: 0.565 AC: 1190 AN: 2108

Alfa AF: 0.648 Hom.: 21142

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
PhyloP100		1.2
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: rs1009840; hg19: chr6-134546685; COSMIC: COSV63278988;