6-154422575-GCG-ACA

Variant names:

• chr6-154422575-GCG-ACA
• NM_173515.4:c.874_876delCGCinsTGT
• CNKSR3 p.Arg292Cys

Variant summary

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

The NM_173515.4(CNKSR3):​c.874_876delCGCinsTGT​(p.Arg292Cys) 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: 32)
• Consequence: CNKSR3 NM_173515.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.50
• Publications: 0 publications found

Genes affected

CNKSR3 (HGNC:23034): (CNKSR family member 3) Predicted to be involved in negative regulation of ERK1 and ERK2 cascade; negative regulation of peptidyl-serine phosphorylation; and positive regulation of sodium ion transport. Predicted to act upstream of or within positive regulation of sodium ion transmembrane transporter activity. Predicted to be located in apical plasma membrane and cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000288520 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173515.4. 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
	CNKSR3	NM_173515.4	MANE Select	c.874_876delCGCinsTGT	p.Arg292Cys	missense	N/A	NP_775786.2	Q6P9H4-1
	CNKSR3	NM_001368116.1		c.892_894delCGCinsTGT	p.Arg298Cys	missense	N/A	NP_001355045.1
	CNKSR3	NM_001368117.1		c.874_876delCGCinsTGT	p.Arg292Cys	missense	N/A	NP_001355046.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNKSR3	ENST00000607772.6	TSL:1 MANE Select	c.874_876delCGCinsTGT	p.Arg292Cys	missense	N/A	ENSP00000475915.1	Q6P9H4-1
	ENSG00000288520	ENST00000673182.1		c.874_876delCGCinsTGT	p.Arg292Cys	missense	N/A	ENSP00000499846.1
	CNKSR3	ENST00000479339.5	TSL:1	c.634_636delCGCinsTGT	p.Arg212Cys	missense	N/A	ENSP00000418975.1	A0A5H1ZRR2

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.5

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: chr6-154743709;