6-134222681-T-C

Variant names:

• chr6-134222681-T-C
• rs1763502
• NM_001143676.3:c.286-15250A>G

Variant summary

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

The NM_001143676.3(SGK1):​c.286-15250A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.594 in 152,054 control chromosomes in the GnomAD database, including 30,153 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 0.59 (30153 hom., cov: 32)
• Consequence: SGK1 NM_001143676.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.480
• Publications: 1 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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.818 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SGK1	NM_001143676.3	c.286-15250A>G		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.286-15250A>G		intron_variant	Intron 2 of 13	1	NM_001143676.3	ENSP00000356832.5

Frequencies

GnomAD3 genomes AF: 0.594 AC: 90276 AN: 151936 Hom.: 30149 Cov.: 32

Gnomad AFR AF: 0.271

Gnomad AMI AF: 0.760

Gnomad AMR AF: 0.578

Gnomad ASJ AF: 0.743

Gnomad EAS AF: 0.710

Gnomad SAS AF: 0.839

Gnomad FIN AF: 0.793

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.726

Gnomad OTH AF: 0.611

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

GnomAD4 genome AF: 0.594 AC: 90292 AN: 152054 Hom.: 30153 Cov.: 32 AF XY: 0.603 AC XY: 44842 AN XY: 74316

African (AFR) AF: 0.271 AC: 11243 AN: 41476

American (AMR) AF: 0.577 AC: 8804 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.743 AC: 2580 AN: 3472

East Asian (EAS) AF: 0.710 AC: 3676 AN: 5178

South Asian (SAS) AF: 0.840 AC: 4049 AN: 4822

European-Finnish (FIN) AF: 0.793 AC: 8385 AN: 10572

Middle Eastern (MID) AF: 0.670 AC: 197 AN: 294

European-Non Finnish (NFE) AF: 0.726 AC: 49373 AN: 67970

Other (OTH) AF: 0.612 AC: 1293 AN: 2112

Alfa AF: 0.648 Hom.: 4228

Bravo AF: 0.560

Asia WGS AF: 0.714 AC: 2482 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	7.4
DANN	Benign	0.78
PhyloP100		0.48
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: rs1763502; hg19: chr6-134543819;