22-39134464-C-A

Variant summary

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

The NM_175709.5(CBX7):​c.535G>T​(p.Ala179Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,455,952 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: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CBX7
NM_175709.5 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.78
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]

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=0.09406251).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CBX7NM_175709.5 linkc.535G>T p.Ala179Ser missense_variant Exon 5 of 6 ENST00000216133.10 NP_783640.1 O95931A0A024R1Q2
CBX7NM_001346743.2 linkc.535G>T p.Ala179Ser missense_variant Exon 5 of 6 NP_001333672.1
CBX7NM_001346744.2 linkc.256G>T p.Ala86Ser missense_variant Exon 5 of 6 NP_001333673.1 Q4PNR6B0QYP2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CBX7ENST00000216133.10 linkc.535G>T p.Ala179Ser missense_variant Exon 5 of 6 1 NM_175709.5 ENSP00000216133.5 O95931

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1455952
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
724562
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:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000378

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Feb 07, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.535G>T (p.A179S) alteration is located in exon 5 (coding exon 5) of the CBX7 gene. This alteration results from a G to T substitution at nucleotide position 535, causing the alanine (A) at amino acid position 179 to be replaced by a serine (S). 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
0.081
BayesDel_addAF
Benign
-0.24
T
BayesDel_noAF
Benign
-0.59
CADD
Benign
16
DANN
Benign
0.93
DEOGEN2
Benign
0.023
T;T
Eigen
Benign
-0.69
Eigen_PC
Benign
-0.61
FATHMM_MKL
Uncertain
0.86
D
LIST_S2
Benign
0.79
T;T
M_CAP
Benign
0.0090
T
MetaRNN
Benign
0.094
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.9
L;.
PrimateAI
Benign
0.45
T
PROVEAN
Benign
-0.12
N;N
REVEL
Benign
0.027
Sift
Benign
0.26
T;T
Sift4G
Benign
0.83
T;T
Polyphen
0.68
P;B
Vest4
0.19
MutPred
0.13
Gain of glycosylation at A179 (P = 0.0112);.;
MVP
0.49
MPC
0.45
ClinPred
0.053
T
GERP RS
2.3
Varity_R
0.037
gMVP
0.35

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.

Other links and lift over

dbSNP: rs1337280833; hg19: chr22-39530469; API