8-66840018-CAA-AAG

Variant names:

• chr8-66840018-CAA-AAG
• NM_001033578.3:c.757_759delCAAinsAAG
• SGK3 p.Gln253Lys

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_001033578.3(SGK3):​c.757_759delCAAinsAAG​(p.Gln253Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 30)
• Consequence: SGK3 NM_001033578.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.25
• Publications: 0 publications found

Genes affected

SGK3 (HGNC:10812): (serum/glucocorticoid regulated kinase family member 3) This gene is a member of the Ser/Thr protein kinase family and encodes a phosphoprotein with a PX (phox homology) domain. The protein phosphorylates several target proteins and has a role in neutral amino acid transport and activation of potassium and chloride channels. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

C8orf44-SGK3 (HGNC:48354): (C8orf44-SGK3 readthrough) This locus represents naturally occurring read-through transcription between the neighboring putative uncharacterized protein C8orf44 (GeneID 56260) and serine/threonine-protein kinase Sgk3 (GeneID 23678) genes on chromosome 8. The read-through transcript produces a protein that shares sequence identity with the downstream gene product. [provided by RefSeq, Feb 2011]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001033578.3. 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
	SGK3	NM_001033578.3	MANE Select	c.757_759delCAAinsAAG	p.Gln253Lys	missense	N/A	NP_001028750.1	Q96BR1-1
	C8orf44-SGK3	NM_001204173.2		c.757_759delCAAinsAAG	p.Gln253Lys	missense	N/A	NP_001191102.1
	SGK3	NM_013257.5		c.757_759delCAAinsAAG	p.Gln253Lys	missense	N/A	NP_037389.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGK3	ENST00000521198.7	TSL:1 MANE Select	c.757_759delCAAinsAAG	p.Gln253Lys	missense	N/A	ENSP00000430463.1	Q96BR1-1
	SGK3	ENST00000345714.8	TSL:1	c.757_759delCAAinsAAG	p.Gln253Lys	missense	N/A	ENSP00000331816.5	Q96BR1-1
	SGK3	ENST00000396596.2	TSL:1	c.757_759delCAAinsAAG	p.Gln253Lys	missense	N/A	ENSP00000379842.1	Q96BR1-1

Frequencies

GnomAD3 genomes Cov.: 30

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

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		9.3

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr8-67752253;