22-39134005-CG-AA

Variant names:

• chr22-39134005-CG-AA
• NM_175709.5:c.641_642delCGinsTT
• CBX7 p.Ala214Val

Variant summary

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

The NM_175709.5(CBX7):​c.641_642delCGinsTT​(p.Ala214Val) variant causes a missense change involving the alteration of a non-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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A214P) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CBX7 NM_175709.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.38
• Publications: 0 publications found

Genes affected

CBX7 (HGNC:1557): (chromobox 7) This gene encodes a protein that contains the CHROMO (CHRomatin Organization MOdifier) domain. The encoded protein is a component of the Polycomb repressive complex 1 (PRC1), and is thought to control the lifespan of several normal human cells. [provided by RefSeq, Oct 2016]

ENSG00000279833 (HGNC:58395):

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_175709.5. 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
	CBX7	NM_175709.5	MANE Select	c.641_642delCGinsTT	p.Ala214Val	missense	N/A	NP_783640.1	O95931
	CBX7	NM_001346743.2		c.638_639delCGinsTT	p.Ala213Val	missense	N/A	NP_001333672.1
	CBX7	NM_001346744.2		c.362_363delCGinsTT	p.Ala121Val	missense	N/A	NP_001333673.1	B0QYP2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CBX7	ENST00000216133.10	TSL:1 MANE Select	c.641_642delCGinsTT	p.Ala214Val	missense	N/A	ENSP00000216133.5	O95931
	CBX7	ENST00000401405.7	TSL:1	c.362_363delCGinsTT	p.Ala121Val	missense	N/A	ENSP00000384035.3	B0QYP2
	CBX7	ENST00000858784.1		c.719_720delCGinsTT	p.Ala240Val	missense	N/A	ENSP00000528843.1

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		2.4

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: chr22-39530010;