Variant chr17-79795291-G-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_020649.3(CBX8):c.514C>G(p.Arg172Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000693 in 1,443,754 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

CBX8
NM_020649.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.712

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]

CBX8 links:

Genome browser will be placed here

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=0.15336737).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CBX8	NM_020649.3 link	c.514C>G	p.Arg172Gly	missense_variant	5/5	ENST00000269385.9	NP_065700.1	Q9HC52

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CBX8	ENST00000269385.9 link	c.514C>G	p.Arg172Gly	missense_variant	5/5	1	NM_020649.3	ENSP00000269385.4	Q9HC52
CBX8	ENST00000413392.5 link	c.484C>G	p.Arg162Gly	missense_variant	5/5	3		ENSP00000405058.1	C9J6K3
CBX8	ENST00000427800.2 link	c.439C>G	p.Arg147Gly	missense_variant	5/5	2		ENSP00000408753.2	C9JM54

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.93e-7

AC:

AN:

1443754

Hom.:

Cov.:

AF XY:

0.00000140

AC XY:

AN XY:

716606

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.06e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 15, 2023

The c.514C>G (p.R172G) alteration is located in exon 5 (coding exon 5) of the CBX8 gene. This alteration results from a C to G substitution at nucleotide position 514, causing the arginine (R) at amino acid position 172 to be replaced by a glycine (G). 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

0.11

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.39

CADD

Benign

7.4

DANN

Benign

0.91

DEOGEN2

Benign

0.086

T;.;T

Eigen

Benign

-0.82

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.85

T;T;D

M_CAP

Benign

0.018

MetaRNN

Benign

0.15

T;T;T

MetaSVM

Benign

-0.81

MutationAssessor

Benign

0.69

N;.;.

PrimateAI

Uncertain

0.76

PROVEAN

Benign

0.13

N;N;N

REVEL

Benign

0.21

Sift

Uncertain

0.013

D;D;D

Sift4G

Benign

0.15

T;T;.

Polyphen

0.99

D;.;.

Vest4

0.35

MutPred

0.24

Gain of loop (P = 0.0079);.;.;

MVP

0.57

MPC

0.39

ClinPred

0.48

GERP RS

-4.2

Varity_R

0.086

gMVP

0.23

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over