6-134178716-T-C

Variant names:

• chr6-134178716-T-C
• rs1763527
• NM_001143676.3:c.362-4130A>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.362-4130A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 152,126 control chromosomes in the GnomAD database, including 14,404 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 0.42 (14404 hom., cov: 33)
• Consequence: SGK1 NM_001143676.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.954
• Publications: 9 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.502 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGK1	NM_001143676.3	MANE Select	c.362-4130A>G		intron	N/A	NP_001137148.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGK1	ENST00000367858.10	TSL:1 MANE Select	c.362-4130A>G		intron	N/A	ENSP00000356832.5
	SGK1	ENST00000944482.1		c.146-4130A>G		intron	N/A	ENSP00000614541.1
	SGK1	ENST00000461976.2	TSL:4	c.269-4130A>G		intron	N/A	ENSP00000435577.1

Frequencies

GnomAD3 genomes AF: 0.423 AC: 64319 AN: 152008 Hom.: 14399 Cov.: 33

Gnomad AFR AF: 0.327

Gnomad AMI AF: 0.682

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.448

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.375

Gnomad FIN AF: 0.464

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.506

Gnomad OTH AF: 0.403

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

GnomAD4 genome AF: 0.423 AC: 64340 AN: 152126 Hom.: 14404 Cov.: 33 AF XY: 0.419 AC XY: 31154 AN XY: 74362

African (AFR) AF: 0.327 AC: 13577 AN: 41484

American (AMR) AF: 0.376 AC: 5752 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.448 AC: 1557 AN: 3472

East Asian (EAS) AF: 0.144 AC: 745 AN: 5180

South Asian (SAS) AF: 0.375 AC: 1810 AN: 4826

European-Finnish (FIN) AF: 0.464 AC: 4911 AN: 10578

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.506 AC: 34416 AN: 67986

Other (OTH) AF: 0.399 AC: 842 AN: 2112

Alfa AF: 0.470 Hom.: 77785

Bravo AF: 0.408

Asia WGS AF: 0.261 AC: 906 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.5
DANN	Benign	0.32
PhyloP100		-0.95
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: rs1763527; hg19: chr6-134499854;