22-39134038-G-T

Position:

• chr22-39134038-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_175709.5(CBX7):​c.609C>A​(p.Asp203Glu) 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: CBX7 NM_175709.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.698

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 (HGNC:):

ACMG classification

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=0.11411908).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CBX7	NM_175709.5	c.609C>A	p.Asp203Glu	missense_variant	6/6	ENST00000216133.10	NP_783640.1
CBX7	NM_001346743.2	c.606C>A	p.Asp202Glu	missense_variant	6/6		NP_001333672.1
CBX7	NM_001346744.2	c.330C>A	p.Asp110Glu	missense_variant	6/6		NP_001333673.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CBX7	ENST00000216133.10	c.609C>A	p.Asp203Glu	missense_variant	6/6	1	NM_175709.5	ENSP00000216133.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 05, 2023

The c.609C>A (p.D203E) alteration is located in exon 6 (coding exon 6) of the CBX7 gene. This alteration results from a C to A substitution at nucleotide position 609, causing the aspartic acid (D) at amino acid position 203 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	0.097
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	14
DANN	Uncertain	1.0
DEOGEN2	Benign	0.033	T;T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.30
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.59	T;T
M_CAP	Benign	0.0068	T
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.90	L;.
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.78	N;N
REVEL	Benign	0.065
Sift	Benign	0.35	T;T
Sift4G	Benign	0.69	T;T
Polyphen		0.0020	B;D
Vest4		0.046
MutPred		0.14		Gain of glycosylation at P208 (P = 0.1376);.;
MVP		0.65
MPC		0.31
ClinPred		0.55	D
GERP RS		0.56
Varity_R		0.061
gMVP		0.22

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: chr22-39530043;