6-134261969-G-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001143676.3(SGK1):c.249C>G(p.Asn83Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,402 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SGK1 NM_001143676.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0450

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

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04330483).
• BP6: Variant 6-134261969-G-C is Benign according to our data. Variant chr6-134261969-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2248545.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SGK1	NM_001143676.3	c.249C>G	p.Asn83Lys	missense_variant	2/14	ENST00000367858.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SGK1	ENST00000367858.10	c.249C>G	p.Asn83Lys	missense_variant	2/14	1	NM_001143676.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461402 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726998

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 01, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
Cadd	Benign	8.4
Dann	Benign	0.66
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.31	T;T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.043	T;T;T
MetaSVM	Benign	-0.95	T
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.38	T
PROVEAN	Benign	0.34	N;N;N
REVEL	Benign	0.059
Sift	Benign	1.0	T;T;T
Sift4G	Benign	0.43	T;T;T
Polyphen		0.0	B;.;B
Vest4		0.084
MutPred		0.26		Gain of ubiquitination at N83 (P = 0.0121);.;Gain of ubiquitination at N83 (P = 0.0121);
MVP		0.18
MPC		0.042
ClinPred		0.29	T
GERP RS		2.8
gMVP		0.082

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-134583107;