17-79795052-GGC-TGT

Variant names:

• chr17-79795052-GGC-TGT
• NM_020649.3:c.751_753delGCCinsACA
• CBX8 p.Ala251Thr

Variant summary

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

The NM_020649.3(CBX8):​c.751_753delGCCinsACA​(p.Ala251Thr) variant causes a missense change. 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: CBX8 NM_020649.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.40
• Publications: 0 publications found

Genes affected

CBX8 (HGNC:15962): (chromobox 8) Enables methylated histone binding activity. Involved in negative regulation of transcription by RNA polymerase II. Located in chromatin and nucleoplasm. Part of PRC1 complex. Biomarker of esophagus squamous cell carcinoma and glioblastoma. [provided by Alliance of Genome Resources, Apr 2022]

CBX8 Gene-Disease associations (from GenCC):

• schizophrenia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020649.3. 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
	CBX8	NM_020649.3	MANE Select	c.751_753delGCCinsACA	p.Ala251Thr	missense	N/A	NP_065700.1	Q9HC52

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CBX8	ENST00000269385.9	TSL:1 MANE Select	c.751_753delGCCinsACA	p.Ala251Thr	missense	N/A	ENSP00000269385.4	Q9HC52
	CBX8	ENST00000413392.5	TSL:3	c.721_723delGCCinsACA	p.Ala241Thr	missense	N/A	ENSP00000405058.1	C9J6K3
	CBX8	ENST00000427800.2	TSL:2	c.*150_*152delGCCinsACA		downstream_gene	N/A	ENSP00000408753.2	C9JM54

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		4.4

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: chr17-77768851;