rs3813344

Positions:

• chr6-134317828-C-G

Variant summary

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

The NM_001143676.3(SGK1):​c.-368G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0794 in 206,858 control chromosomes in the GnomAD database, including 771 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 0.074 (490 hom., cov: 32)
  • Exomes 𝑓: 0.096 (281 hom.)
• Consequence: SGK1 NM_001143676.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.284

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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0999 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SGK1	NM_001143676.3	c.-368G>C		5_prime_UTR_variant	1/14	ENST00000367858.10	NP_001137148.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SGK1	ENST00000367858.10	c.-368G>C		5_prime_UTR_variant	1/14	1	NM_001143676.3	ENSP00000356832.5
SGK1	ENST00000461976.2	c.-38G>C		5_prime_UTR_variant	1/6	4		ENSP00000435577.1
SGK1	ENST00000533224.1	c.-96G>C		5_prime_UTR_variant	1/3	4		ENSP00000436470.1

Frequencies

GnomAD3 genomes AF: 0.0736 AC: 11207 AN: 152168 Hom.: 488 Cov.: 32

Gnomad AFR AF: 0.0217

Gnomad AMI AF: 0.0581

Gnomad AMR AF: 0.0652

Gnomad ASJ AF: 0.0995

Gnomad EAS AF: 0.0688

Gnomad SAS AF: 0.0845

Gnomad FIN AF: 0.0956

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.0789

GnomAD4 exome AF: 0.0956 AC: 5218 AN: 54572 Hom.: 281 Cov.: 0 AF XY: 0.0961 AC XY: 2667 AN XY: 27754

Gnomad4 AFR exome AF: 0.0252

Gnomad4 AMR exome AF: 0.0827

Gnomad4 ASJ exome AF: 0.114

Gnomad4 EAS exome AF: 0.0789

Gnomad4 SAS exome AF: 0.0807

Gnomad4 FIN exome AF: 0.102

Gnomad4 NFE exome AF: 0.102

Gnomad4 OTH exome AF: 0.0928

GnomAD4 genome AF: 0.0736 AC: 11201 AN: 152286 Hom.: 490 Cov.: 32 AF XY: 0.0745 AC XY: 5548 AN XY: 74458

Gnomad4 AFR AF: 0.0218

Gnomad4 AMR AF: 0.0652

Gnomad4 ASJ AF: 0.0995

Gnomad4 EAS AF: 0.0682

Gnomad4 SAS AF: 0.0844

Gnomad4 FIN AF: 0.0956

Gnomad4 NFE AF: 0.102

Gnomad4 OTH AF: 0.0776

Alfa AF: 0.0788 Hom.: 62

Bravo AF: 0.0694

Asia WGS AF: 0.0630 AC: 219 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	9.7
DANN	Benign	0.76

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3813344; hg19: chr6-134638966; COSMIC: COSV63276233; COSMIC: COSV63276233;