6-134172259-G-C

Variant names:

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

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001143676.3(SGK1):​c.1005C>G​(p.Asp335Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SGK1 NM_001143676.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.00
• Publications: 0 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: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.992

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>G	p.Asp335Glu	missense	Exon 10 of 14	NP_001137148.1
	SGK1	NM_001143677.2		c.804C>G	p.Asp268Glu	missense	Exon 8 of 12	NP_001137149.1
	SGK1	NM_001143678.2		c.762C>G	p.Asp254Glu	missense	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>G	p.Asp335Glu	missense	Exon 10 of 14	ENSP00000356832.5
	SGK1	ENST00000528577.5	TSL:1	c.804C>G	p.Asp268Glu	missense	Exon 8 of 12	ENSP00000434450.1
	SGK1	ENST00000413996.7	TSL:1	c.762C>G	p.Asp254Glu	missense	Exon 8 of 12	ENSP00000396242.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.49	D
BayesDel_noAF	Pathogenic	0.47
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.60	D
Eigen	Pathogenic	0.71
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Pathogenic	0.53	D
MetaRNN	Pathogenic	0.99	D
MetaSVM	Pathogenic	1.0	D
MutationAssessor	Pathogenic	3.9	H
PhyloP100		4.0
PrimateAI	Pathogenic	0.89	D
PROVEAN	Uncertain	-3.9	D
REVEL	Pathogenic	0.92
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.91
MutPred		0.93		Loss of ubiquitination at K245 (P = 0.0896)
MVP		0.98
MPC		1.7
ClinPred		1.0	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.87
gMVP		0.93
Mutation Taster		=25/75	disease causing

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;