rs202240562

Positions:

chrX-40074082-T-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001123385.2(BCOR):c.1264A>G(p.Ser422Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000297 in 1,210,811 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 9 hemizygotes in GnomAD. 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: 𝑓 0.000089 ( 0 hom., 2 hem., cov: 25)

Exomes 𝑓: 0.000024 ( 0 hom. 7 hem. )

Consequence

BCOR
NM_001123385.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1O:1

Conservation

PhyloP100: 0.332

Variant links:

Genes affected

BCOR (HGNC:20893): (BCL6 corepressor) The protein encoded by this gene was identified as an interacting corepressor of BCL6, a POZ/zinc finger transcription repressor that is required for germinal center formation and may influence apoptosis. This protein selectively interacts with the POZ domain of BCL6, but not with eight other POZ proteins. Specific class I and II histone deacetylases (HDACs) have been shown to interact with this protein, which suggests a possible link between the two classes of HDACs. Several transcript variants encoding different isoforms have been found for this gene. A pseudogene of this gene is found on chromosome Y.[provided by RefSeq, Jun 2010]

BCOR links:

BCOR (HGNC:):

BCOR links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.016260564).

BS2

High Hemizygotes in GnomAd4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCOR	NM_001123385.2 linkuse as main transcript	c.1264A>G	p.Ser422Gly	missense_variant	4/15	ENST00000378444.9	NP_001116857.1	Q6W2J9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BCOR	ENST00000378444.9 linkuse as main transcript	c.1264A>G	p.Ser422Gly	missense_variant	4/15	1	NM_001123385.2	ENSP00000367705.4		Q6W2J9-1

Frequencies

GnomAD3 genomes

AF:

0.0000888

AC:

AN:

112669

Hom.:

Cov.:

AF XY:

0.0000575

AC XY:

AN XY:

34803

show subpopulations

Gnomad AFR

AF:

0.000322

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000219

AC:

AN:

183002

Hom.:

AF XY:

0.0000296

AC XY:

AN XY:

67480

show subpopulations

Gnomad AFR exome

AF:

0.000305

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

AF:

0.0000237

AC:

AN:

1098088

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

363450

show subpopulations

Gnomad4 AFR exome

AF:

0.000909

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:

0.00000119

Gnomad4 OTH exome

AF:

0.0000217

GnomAD4 genome

AF:

0.0000887

AC:

AN:

112723

Hom.:

Cov.:

AF XY:

0.0000574

AC XY:

AN XY:

34867

show subpopulations

Gnomad4 AFR

AF:

0.000321

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000136

Hom.:

Bravo

AF:

0.000166

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1Other:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Oculofaciocardiodental syndrome

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Apr 02, 2023

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The glycine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 133678). This variant has not been reported in the literature in individuals affected with BCOR-related conditions. This variant is present in population databases (rs202240562, gnomAD 0.03%). This sequence change replaces serine, which is neutral and polar, with glycine, which is neutral and non-polar, at codon 422 of the BCOR protein (p.Ser422Gly). -

not specified

Other:1

not provided, no classification provided

reference population

ITMI

Sep 19, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.047

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.25

DANN

Benign

0.38

DEOGEN2

Benign

0.16

.;.;T;.;T

FATHMM_MKL

Benign

0.37

LIST_S2

Benign

0.64

.;T;T;T;T

M_CAP

Benign

0.0031

MetaRNN

Benign

0.016

T;T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-1.6

N;N;N;N;.

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.2

N;N;N;N;N

REVEL

Benign

0.039

Sift

Benign

0.76

T;T;T;T;T

Sift4G

Benign

0.54

T;T;T;T;.

Polyphen

0.0

B;B;B;B;.

Vest4

0.040

MutPred

0.13

Loss of phosphorylation at S422 (P = 0.0242);Loss of phosphorylation at S422 (P = 0.0242);Loss of phosphorylation at S422 (P = 0.0242);Loss of phosphorylation at S422 (P = 0.0242);Loss of phosphorylation at S422 (P = 0.0242);

MVP

0.21

MPC

0.24

ClinPred

0.0077

GERP RS

-2.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.055

gMVP

0.036

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