17-79795167-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020649.3(CBX8):​c.638G>A​(p.Arg213Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

CBX8
NM_020649.3 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.30
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.1938195).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CBX8NM_020649.3 linkc.638G>A p.Arg213Lys missense_variant Exon 5 of 5 ENST00000269385.9 NP_065700.1 Q9HC52

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CBX8ENST00000269385.9 linkc.638G>A p.Arg213Lys missense_variant Exon 5 of 5 1 NM_020649.3 ENSP00000269385.4 Q9HC52
CBX8ENST00000413392.5 linkc.608G>A p.Arg203Lys missense_variant Exon 5 of 5 3 ENSP00000405058.1 C9J6K3
CBX8ENST00000427800.2 linkc.*37G>A downstream_gene_variant 2 ENSP00000408753.2 C9JM54
CBX8ENST00000485449.1 linkn.*227G>A downstream_gene_variant 3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
35
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 18, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.638G>A (p.R213K) alteration is located in exon 5 (coding exon 5) of the CBX8 gene. This alteration results from a G to A substitution at nucleotide position 638, causing the arginine (R) at amino acid position 213 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.092
BayesDel_addAF
Benign
-0.079
T
BayesDel_noAF
Benign
-0.35
CADD
Benign
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.065
T;.
Eigen
Benign
-0.011
Eigen_PC
Benign
0.059
FATHMM_MKL
Uncertain
0.87
D
LIST_S2
Benign
0.76
T;T
M_CAP
Benign
0.014
T
MetaRNN
Benign
0.19
T;T
MetaSVM
Benign
-0.83
T
MutationAssessor
Benign
1.2
L;.
PrimateAI
Uncertain
0.70
T
PROVEAN
Benign
-0.68
N;N
REVEL
Benign
0.19
Sift
Uncertain
0.016
D;D
Sift4G
Benign
0.70
T;T
Polyphen
0.82
P;.
Vest4
0.34
MutPred
0.36
Gain of ubiquitination at R213 (P = 0.0077);.;
MVP
0.50
MPC
0.24
ClinPred
0.39
T
GERP RS
4.9
Varity_R
0.21
gMVP
0.25

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-77768966; API