22-39134036-A-G

Position:

• chr22-39134036-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_175709.5(CBX7):​c.611T>C​(p.Leu204Pro) 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. 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)
• Consequence: CBX7 NM_175709.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.928

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05372244).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CBX7	NM_175709.5	c.611T>C	p.Leu204Pro	missense_variant	6/6	ENST00000216133.10	NP_783640.1
CBX7	NM_001346743.2	c.608T>C	p.Leu203Pro	missense_variant	6/6		NP_001333672.1
CBX7	NM_001346744.2	c.332T>C	p.Leu111Pro	missense_variant	6/6		NP_001333673.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CBX7	ENST00000216133.10	c.611T>C	p.Leu204Pro	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

Feb 15, 2023

The c.611T>C (p.L204P) alteration is located in exon 6 (coding exon 6) of the CBX7 gene. This alteration results from a T to C substitution at nucleotide position 611, causing the leucine (L) at amino acid position 204 to be replaced by a proline (P). 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	0.064
BayesDel_addAF	Benign	-0.093	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	19
DANN	Benign	0.93
DEOGEN2	Benign	0.034	T;T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.56	T;T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.054	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.95	L;.
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	0.050	N;N
REVEL	Benign	0.043
Sift	Benign	0.28	T;T
Sift4G	Benign	0.26	T;T
Polyphen		0.0010	B;P
Vest4		0.13
MutPred		0.19		Loss of stability (P = 0.0497);.;
MVP		0.44
MPC		1.4
ClinPred		0.68	D
GERP RS		3.0
Varity_R		0.10
gMVP		0.39

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: chr22-39530041;