Variant 22-39134644-T-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_175709.5(CBX7):c.355A>G(p.Lys119Glu) 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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CBX7
NM_175709.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.71

Variant links:

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]

CBX7 links:

CBX7 (HGNC:):

CBX7 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=0.15437415).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CBX7	NM_175709.5 linkuse as main transcript	c.355A>G	p.Lys119Glu	missense_variant	5/6	ENST00000216133.10	NP_783640.1	O95931A0A024R1Q2
CBX7	NM_001346743.2 linkuse as main transcript	c.355A>G	p.Lys119Glu	missense_variant	5/6		NP_001333672.1
CBX7	NM_001346744.2 linkuse as main transcript	c.247-171A>G		intron_variant			NP_001333673.1	Q4PNR6B0QYP2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CBX7	ENST00000216133.10 linkuse as main transcript	c.355A>G	p.Lys119Glu	missense_variant	5/6	1	NM_175709.5	ENSP00000216133.5		O95931

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000487

AC:

AN:

205326

Hom.:

AF XY:

0.00

AC XY:

AN XY:

111860

show subpopulations

Gnomad AFR exome

AF:

0.0000802

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1436418

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

711840

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000227

ExAC

AF:

0.00000830

AC:

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

Mar 01, 2024

The c.355A>G (p.K119E) alteration is located in exon 5 (coding exon 5) of the CBX7 gene. This alteration results from a A to G substitution at nucleotide position 355, causing the lysine (K) at amino acid position 119 to be replaced by a glutamic acid (E). 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

0.12

BayesDel_addAF

Benign

-0.017

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.029

T;.

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.17

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.74

T;T

M_CAP

Benign

0.0040

MetaRNN

Benign

0.15

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.8

L;.

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-0.58

N;N

REVEL

Benign

0.26

Sift

Benign

0.18

T;D

Sift4G

Benign

0.60

T;.

Polyphen

0.65

P;.

Vest4

0.56

MutPred

0.23

Loss of ubiquitination at K119 (P = 0.0023);.;

MVP

0.56

MPC

0.49

ClinPred

0.11

GERP RS

3.9

Varity_R

0.10

gMVP

0.58

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over