Variant 17-48076041-T-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000225603.9(CBX1):c.278A>T(p.Asp93Val) 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 1,460,468 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CBX1
ENST00000225603.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.41

Variant links:

Genes affected

CBX1 (HGNC:1551): (chromobox 1) This gene encodes a highly conserved nonhistone protein, which is a member of the heterochromatin protein family . The protein is enriched in the heterochromatin and associated with centromeres. The protein has a single N-terminal chromodomain which can bind to histone proteins via methylated lysine residues, and a C-terminal chromo shadow-domain (CSD) which is responsible for the homodimerization and interaction with a number of chromatin-associated nonhistone proteins. The protein may play an important role in the epigenetic control of chromatin structure and gene expression. Several related pseudogenes are located on chromosomes 1, 3, and X. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Jul 2008]

CBX1 links:

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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=0.10464537).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CBX1	NM_001127228.2 linkuse as main transcript	c.278A>T	p.Asp93Val	missense_variant	3/5	ENST00000225603.9	NP_001120700.1
CBX1	NM_006807.5 linkuse as main transcript	c.278A>T	p.Asp93Val	missense_variant	3/5		NP_006798.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CBX1	ENST00000225603.9 linkuse as main transcript	c.278A>T	p.Asp93Val	missense_variant	3/5	1	NM_001127228.2	ENSP00000225603	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1460468

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726428

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:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

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 16, 2022

The c.278A>T (p.D93V) alteration is located in exon 3 (coding exon 2) of the CBX1 gene. This alteration results from a A to T substitution at nucleotide position 278, causing the aspartic acid (D) at amino acid position 93 to be replaced by a valine (V). 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

0.13

BayesDel_addAF

Benign

-0.094

BayesDel_noAF

Benign

-0.37

CADD

Uncertain

DANN

Benign

0.97

DEOGEN2

Benign

0.17

T;T;.;T;T;.

Eigen

Benign

-0.18

Eigen_PC

Benign

0.056

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.78

.;T;T;T;T;T

M_CAP

Benign

0.0021

MetaRNN

Benign

0.10

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

N;N;.;.;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-1.7

N;N;.;N;.;N

REVEL

Benign

0.033

Sift

Benign

0.15

T;T;.;T;.;T

Sift4G

Benign

0.22

T;T;.;.;T;T

Polyphen

0.0

B;B;.;.;.;.

Vest4

0.33

MutPred

0.29

Gain of methylation at K94 (P = 0.0393);Gain of methylation at K94 (P = 0.0393);Gain of methylation at K94 (P = 0.0393);Gain of methylation at K94 (P = 0.0393);Gain of methylation at K94 (P = 0.0393);Gain of methylation at K94 (P = 0.0393);

MVP

0.35

MPC

1.8

ClinPred

0.44

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.096

gMVP

0.36

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