rs7755303

Variant names:

• chr6-134170319-G-A
• rs7755303
• NM_001143676.3:c.1530C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-134170319-G-A
• chr6-134170319-G-C

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_001143676.3(SGK1):​c.1530C>T​(p.Ala510Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000906 in 1,613,950 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0045 (6 hom., cov: 32)
  • Exomes 𝑓: 0.00053 (6 hom.)
• Consequence: SGK1 NM_001143676.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.48
• Publications: 4 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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 6-134170319-G-A is Benign according to our data. Variant chr6-134170319-G-A is described in ClinVar as Benign. ClinVar VariationId is 769694.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-4.48 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAdExome4 allele frequency = 0.000528 (772/1461714) while in subpopulation AFR AF = 0.0174 (581/33478). AF 95% confidence interval is 0.0162. There are 6 homozygotes in GnomAdExome4. There are 349 alleles in the male GnomAdExome4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 691 AD gene.

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.1530C>T	p.Ala510Ala	synonymous	Exon 14 of 14	NP_001137148.1	O00141-2
	SGK1	NM_001143677.2		c.1329C>T	p.Ala443Ala	synonymous	Exon 12 of 12	NP_001137149.1	O00141-5
	SGK1	NM_001143678.2		c.1287C>T	p.Ala429Ala	synonymous	Exon 12 of 12	NP_001137150.1	O00141-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGK1	ENST00000367858.10	TSL:1 MANE Select	c.1530C>T	p.Ala510Ala	synonymous	Exon 14 of 14	ENSP00000356832.5	O00141-2
	SGK1	ENST00000528577.5	TSL:1	c.1329C>T	p.Ala443Ala	synonymous	Exon 12 of 12	ENSP00000434450.1	O00141-5
	SGK1	ENST00000413996.7	TSL:1	c.1287C>T	p.Ala429Ala	synonymous	Exon 12 of 12	ENSP00000396242.3	O00141-3

Frequencies

GnomAD3 genomes AF: 0.00454 AC: 690 AN: 152118 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.0160

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000982

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00336

GnomAD2 exomes AF: 0.00133 AC: 334 AN: 251452 AF XY: 0.00103

Gnomad AFR exome AF: 0.0178

Gnomad AMR exome AF: 0.000723

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000139

Gnomad NFE exome AF: 0.0000879

Gnomad OTH exome AF: 0.000489

GnomAD4 exome AF: 0.000528 AC: 772 AN: 1461714 Hom.: 6 Cov.: 31 AF XY: 0.000480 AC XY: 349 AN XY: 727176

African (AFR) AF: 0.0174 AC: 581 AN: 33478

American (AMR) AF: 0.000738 AC: 33 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000580 AC: 5 AN: 86252

European-Finnish (FIN) AF: 0.0000562 AC: 3 AN: 53410

Middle Eastern (MID) AF: 0.00122 AC: 7 AN: 5760

European-Non Finnish (NFE) AF: 0.0000719 AC: 80 AN: 1111890

Other (OTH) AF: 0.00104 AC: 63 AN: 60388

GnomAD4 genome AF: 0.00454 AC: 691 AN: 152236 Hom.: 6 Cov.: 32 AF XY: 0.00443 AC XY: 330 AN XY: 74456

African (AFR) AF: 0.0159 AC: 662 AN: 41540

American (AMR) AF: 0.000980 AC: 15 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.0000943 AC: 1 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68004

Other (OTH) AF: 0.00332 AC: 7 AN: 2108

Alfa AF: 0.00364 Hom.: 7

Bravo AF: 0.00496

Asia WGS AF: 0.00260 AC: 9 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.078
DANN	Benign	0.87
PhyloP100		-4.5
Mutation Taster		=99/1	polymorphism

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: rs7755303; hg19: chr6-134491457;