NM_001143676.3:c.285+6560A>G

Variant names:

• chr6-134255373-T-C
• rs9493873
• NM_001143676.3:c.285+6560A>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.285+6560A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0406 in 151,954 control chromosomes in the GnomAD database, including 222 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 0.041 (222 hom., cov: 31)
• Consequence: SGK1 NM_001143676.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0340
• Publications: 7 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=-0.5).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SGK1	NM_001143676.3	c.285+6560A>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.285+6560A>G		intron_variant	Intron 2 of 13	1	NM_001143676.3	ENSP00000356832.5
SGK1	ENST00000461976.2	c.192+6560A>G		intron_variant	Intron 2 of 5	4		ENSP00000435577.1
SGK1	ENST00000460769.1	c.126+6560A>G		intron_variant	Intron 1 of 1	3		ENSP00000431705.1
SGK1	ENST00000484353.1	n.85+6560A>G		intron_variant	Intron 1 of 2	5

Frequencies

GnomAD3 genomes AF: 0.0406 AC: 6161 AN: 151836 Hom.: 224 Cov.: 31

Gnomad AFR AF: 0.0576

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.0798

Gnomad ASJ AF: 0.0133

Gnomad EAS AF: 0.116

Gnomad SAS AF: 0.0849

Gnomad FIN AF: 0.0192

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0178

Gnomad OTH AF: 0.0408

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

GnomAD4 genome AF: 0.0406 AC: 6166 AN: 151954 Hom.: 222 Cov.: 31 AF XY: 0.0418 AC XY: 3101 AN XY: 74274

African (AFR) AF: 0.0576 AC: 2387 AN: 41456

American (AMR) AF: 0.0798 AC: 1216 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.0133 AC: 46 AN: 3466

East Asian (EAS) AF: 0.116 AC: 593 AN: 5126

South Asian (SAS) AF: 0.0850 AC: 408 AN: 4802

European-Finnish (FIN) AF: 0.0192 AC: 203 AN: 10572

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0179 AC: 1214 AN: 67990

Other (OTH) AF: 0.0399 AC: 84 AN: 2106

Alfa AF: 0.0298 Hom.: 343

Bravo AF: 0.0470

Asia WGS AF: 0.0910 AC: 316 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	11
DANN	Benign	0.93
PhyloP100		0.034
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: rs9493873; hg19: chr6-134576511;