6-134222681-T-C

Position:

• chr6-134222681-T-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.86).
• 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/exons	MANE	Protein	UniProt
SGK1	NM_001143676.3	c.286-15250A>G		intron_variant		ENST00000367858.10	NP_001137148.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SGK1	ENST00000367858.10	c.286-15250A>G		intron_variant		1	NM_001143676.3	ENSP00000356832

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

Gnomad4 AFR AF: 0.271

Gnomad4 AMR AF: 0.577

Gnomad4 ASJ AF: 0.743

Gnomad4 EAS AF: 0.710

Gnomad4 SAS AF: 0.840

Gnomad4 FIN AF: 0.793

Gnomad4 NFE AF: 0.726

Gnomad4 OTH AF: 0.612

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1763502; hg19: chr6-134543819;