6-134172259-G-A

Variant names:

• chr6-134172259-G-A
• rs1057293
• NM_001143676.3:c.1005C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001143676.3(SGK1):​c.1005C>T​(p.Asp335Asp) variant causes a synonymous change. The variant allele was found at a frequency of 0.106 in 1,613,382 control chromosomes in the GnomAD database, including 9,780 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 0.11 (956 hom., cov: 33)
  • Exomes 𝑓: 0.11 (8824 hom.)
• Consequence: SGK1 NM_001143676.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.00
• Publications: 34 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001143676.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGK1	NM_001143676.3	MANE Select	c.1005C>T	p.Asp335Asp	synonymous	Exon 10 of 14	NP_001137148.1
	SGK1	NM_001143677.2		c.804C>T	p.Asp268Asp	synonymous	Exon 8 of 12	NP_001137149.1
	SGK1	NM_001143678.2		c.762C>T	p.Asp254Asp	synonymous	Exon 8 of 12	NP_001137150.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGK1	ENST00000367858.10	TSL:1 MANE Select	c.1005C>T	p.Asp335Asp	synonymous	Exon 10 of 14	ENSP00000356832.5
	SGK1	ENST00000528577.5	TSL:1	c.804C>T	p.Asp268Asp	synonymous	Exon 8 of 12	ENSP00000434450.1
	SGK1	ENST00000413996.7	TSL:1	c.762C>T	p.Asp254Asp	synonymous	Exon 8 of 12	ENSP00000396242.3

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16580 AN: 152096 Hom.: 952 Cov.: 33

Gnomad AFR AF: 0.0948

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.196

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0995

Gnomad OTH AF: 0.104

GnomAD2 exomes AF: 0.124 AC: 31078 AN: 251264 AF XY: 0.120

Gnomad AFR exome AF: 0.0949

Gnomad AMR exome AF: 0.206

Gnomad ASJ exome AF: 0.129

Gnomad EAS exome AF: 0.205

Gnomad FIN exome AF: 0.126

Gnomad NFE exome AF: 0.0958

Gnomad OTH exome AF: 0.114

GnomAD4 exome AF: 0.106 AC: 154181 AN: 1461168 Hom.: 8824 Cov.: 31 AF XY: 0.105 AC XY: 76261 AN XY: 726918

African (AFR) AF: 0.0914 AC: 3058 AN: 33466

American (AMR) AF: 0.199 AC: 8885 AN: 44636

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 3258 AN: 26114

East Asian (EAS) AF: 0.187 AC: 7407 AN: 39688

South Asian (SAS) AF: 0.102 AC: 8796 AN: 86200

European-Finnish (FIN) AF: 0.125 AC: 6692 AN: 53412

Middle Eastern (MID) AF: 0.0664 AC: 383 AN: 5768

European-Non Finnish (NFE) AF: 0.0979 AC: 108865 AN: 1111530

Other (OTH) AF: 0.113 AC: 6837 AN: 60354

GnomAD4 genome AF: 0.109 AC: 16600 AN: 152214 Hom.: 956 Cov.: 33 AF XY: 0.111 AC XY: 8292 AN XY: 74410

African (AFR) AF: 0.0948 AC: 3939 AN: 41534

American (AMR) AF: 0.155 AC: 2365 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.128 AC: 445 AN: 3466

East Asian (EAS) AF: 0.196 AC: 1013 AN: 5172

South Asian (SAS) AF: 0.100 AC: 485 AN: 4830

European-Finnish (FIN) AF: 0.123 AC: 1301 AN: 10592

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0995 AC: 6765 AN: 68016

Other (OTH) AF: 0.103 AC: 218 AN: 2112

Alfa AF: 0.104 Hom.: 2924

Bravo AF: 0.111

Asia WGS AF: 0.149 AC: 517 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	13
DANN	Benign	0.91
PhyloP100		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=96/4	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1057293; hg19: chr6-134493397; COSMIC: COSV52804340; COSMIC: COSV52804340;