chr6-134170860-T-C

Variant names:

• chr6-134170860-T-C
• rs1171390403
• NM_001143676.3:c.1379A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 1P and 5B. PP5 BP4 BS2

The NM_001143676.3(SGK1):​c.1379A>G​(p.Asn460Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000548 in 1,459,214 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (no stars).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: SGK1 NM_001143676.3 missense
• Clinical Significance: Likely pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 5.08
• Publications: 1 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_benign. The variant received -4 ACMG points.

• PP5: Variant 6-134170860-T-C is Pathogenic according to our data. Variant chr6-134170860-T-C is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 800349.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP4: Computational evidence support a benign effect (MetaRNN=0.18355492). . Strength limited to SUPPORTING due to the PP5.
• BS2: High AC in GnomAdExome4 at 8 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.1379A>G	p.Asn460Ser	missense	Exon 13 of 14	NP_001137148.1	O00141-2
	SGK1	NM_001143677.2		c.1178A>G	p.Asn393Ser	missense	Exon 11 of 12	NP_001137149.1	O00141-5
	SGK1	NM_001143678.2		c.1136A>G	p.Asn379Ser	missense	Exon 11 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.1379A>G	p.Asn460Ser	missense	Exon 13 of 14	ENSP00000356832.5	O00141-2
	SGK1	ENST00000528577.5	TSL:1	c.1178A>G	p.Asn393Ser	missense	Exon 11 of 12	ENSP00000434450.1	O00141-5
	SGK1	ENST00000413996.7	TSL:1	c.1136A>G	p.Asn379Ser	missense	Exon 11 of 12	ENSP00000396242.3	O00141-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251374 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000548 AC: 8 AN: 1459214 Hom.: 0 Cov.: 29 AF XY: 0.00000551 AC XY: 4 AN XY: 726218

African (AFR) AF: 0.00 AC: 0 AN: 33424

American (AMR) AF: 0.00 AC: 0 AN: 44712

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86186

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1109600

Other (OTH) AF: 0.0000166 AC: 1 AN: 60310

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000282 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Likely pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Multiple myeloma (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.057
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.35	T
Eigen	Benign	0.011
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L
PhyloP100		5.1
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.48	N
REVEL	Benign	0.049
Sift	Benign	0.18	T
Sift4G	Benign	0.65	T
Polyphen		0.0	B
Vest4		0.27
MutPred		0.27		Gain of catalytic residue at K366 (P = 0.0071)
MVP		0.50
MPC		0.56
ClinPred		0.27	T
GERP RS		6.0
Varity_R		0.16
gMVP		0.42
Mutation Taster		=75/25	disease causing (ClinVar)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1171390403; hg19: chr6-134491998;