rs587778093

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001123385.2(BCOR):c.2954A>T(p.Tyr985Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000108 in 1,208,648 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.000045 ( 0 hom., 1 hem., cov: 24)

Exomes 𝑓: 0.0000073 ( 0 hom. 3 hem. )

Consequence

BCOR
NM_001123385.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2O:1

Conservation

PhyloP100: 5.87

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.25791258).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BCOR	NM_001123385.2 linkuse as main transcript	c.2954A>T	p.Tyr985Phe	missense_variant	4/15	ENST00000378444.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCOR	ENST00000378444.9 linkuse as main transcript	c.2954A>T	p.Tyr985Phe	missense_variant	4/15	1	NM_001123385.2	P2	Q6W2J9-1

Frequencies

GnomAD3 genomes

AF:

0.0000446

AC:

AN:

112163

Hom.:

Cov.:

AF XY:

0.0000291

AC XY:

AN XY:

34311

show subpopulations

Gnomad AFR

AF:

0.000162

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:

0.00000562

AC:

AN:

177824

Hom.:

AF XY:

0.0000159

AC XY:

AN XY:

62764

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000369

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:

0.00000730

AC:

AN:

1096485

Hom.:

Cov.:

AF XY:

0.00000829

AC XY:

AN XY:

361941

show subpopulations

Gnomad4 AFR exome

AF:

0.000190

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000186

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000119

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000446

AC:

AN:

112163

Hom.:

Cov.:

AF XY:

0.0000291

AC XY:

AN XY:

34311

show subpopulations

Gnomad4 AFR

AF:

0.000162

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

Bravo

AF:

0.0000453

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 13, 2021

The c.2954A>T (p.Y985F) alteration is located in exon 4 (coding exon 3) of the BCOR gene. This alteration results from a A to T substitution at nucleotide position 2954, causing the tyrosine (Y) at amino acid position 985 to be replaced by a phenylalanine (F). The p.Y985F alteration is predicted to be tolerated by in silico analysis. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Oculofaciocardiodental syndrome

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Invitae

Nov 15, 2022

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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). ClinVar contains an entry for this variant (Variation ID: 133679). This variant has not been reported in the literature in individuals affected with BCOR-related conditions. This variant is present in population databases (rs587778093, gnomAD 0.006%). This sequence change replaces tyrosine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 985 of the BCOR protein (p.Tyr985Phe). -

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

Pathogenic

0.56

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.46

Cadd

Uncertain

Dann

Uncertain

0.99

FATHMM_MKL

Uncertain

0.96

M_CAP

Benign

0.084

MetaRNN

Benign

0.26

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

M;M;M;M;.;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-2.1

N;N;N;N;D;.

REVEL

Benign

0.19

Sift

Pathogenic

0.0

D;D;D;D;D;.

Sift4G

Benign

0.17

T;T;T;T;.;D

Polyphen

1.0

D;D;D;D;.;.

Vest4

0.57

MutPred

0.24

Loss of phosphorylation at Y985 (P = 0.026);Loss of phosphorylation at Y985 (P = 0.026);Loss of phosphorylation at Y985 (P = 0.026);Loss of phosphorylation at Y985 (P = 0.026);Loss of phosphorylation at Y985 (P = 0.026);.;

MVP

0.49

MPC

0.88

ClinPred

0.59

GERP RS

5.9

Varity_R

0.49

gMVP

0.58

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