chrX-40062275-G-T
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP5BP4BS2
The NM_001123385.2(BCOR):c.4292C>A(p.Ser1431Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.0000223 in 1,209,005 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 6 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.000054 ( 0 hom., 2 hem., cov: 21)
Exomes 𝑓: 0.000019 ( 0 hom. 4 hem. )
Consequence
BCOR
NM_001123385.2 missense
NM_001123385.2 missense
Scores
1
5
9
Clinical Significance
Conservation
PhyloP100: 5.45
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
PP5
?
Variant X-40062275-G-T is Pathogenic according to our data. Variant chrX-40062275-G-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 402203.We mark this variant Likely_pathogenic, oryginal submissions are: {Uncertain_significance=2, Likely_pathogenic=1}. Variant chrX-40062275-G-T is described in Lovd as [Pathogenic].
BP4
?
Computational evidence support a benign effect (MetaRNN=0.20105365).. Strength limited to SUPPORTING due to the PP5.
BS2
?
High Hemizygotes in GnomAd at 2 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BCOR | NM_001123385.2 | c.4292C>A | p.Ser1431Tyr | missense_variant | 10/15 | ENST00000378444.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BCOR | ENST00000378444.9 | c.4292C>A | p.Ser1431Tyr | missense_variant | 10/15 | 1 | NM_001123385.2 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000538 AC: 6AN: 111557Hom.: 0 Cov.: 21 AF XY: 0.0000593 AC XY: 2AN XY: 33727
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000445 AC: 8AN: 179944Hom.: 0 AF XY: 0.0000462 AC XY: 3AN XY: 64982
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GnomAD4 exome AF: 0.0000191 AC: 21AN: 1097448Hom.: 0 Cov.: 33 AF XY: 0.0000110 AC XY: 4AN XY: 362842
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GnomAD4 genome ? AF: 0.0000538 AC: 6AN: 111557Hom.: 0 Cov.: 21 AF XY: 0.0000593 AC XY: 2AN XY: 33727
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Pathogenic:1Uncertain:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Abnormal brain morphology Pathogenic:1
Likely pathogenic, criteria provided, single submitter | research | Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine | - | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Mendelics | May 04, 2022 | - - |
Oculofaciocardiodental syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center | Mar 26, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;.;D;D;D;D
M_CAP
Pathogenic
D
MetaRNN
Benign
T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
N;N;N;N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N;N;N;N;N
REVEL
Benign
Sift
Uncertain
D;D;D;D;D;D;D
Sift4G
Uncertain
D;D;D;D;D;D;D
Polyphen
0.65, 0.66
.;.;P;P;P;P;.
Vest4
0.72, 0.30, 0.34, 0.33, 0.29
MVP
MPC
0.56
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at