chrX-40064561-C-G

Variant summary

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

The NM_001123385.2(BCOR):ā€‹c.3277G>Cā€‹(p.Glu1093Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000000911 in 1,098,135 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E1093K) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 24)
Exomes š‘“: 9.1e-7 ( 0 hom. 0 hem. )

Consequence

BCOR
NM_001123385.2 missense

Scores

5
12

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.51
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]

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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=0.22051218).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
BCORNM_001123385.2 linkuse as main transcriptc.3277G>C p.Glu1093Gln missense_variant 7/15 ENST00000378444.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
BCORENST00000378444.9 linkuse as main transcriptc.3277G>C p.Glu1093Gln missense_variant 7/151 NM_001123385.2 P2Q6W2J9-1

Frequencies

GnomAD3 genomes
Cov.:
24
GnomAD4 exome
AF:
9.11e-7
AC:
1
AN:
1098135
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
363491
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000119
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.13
BayesDel_addAF
Benign
-0.20
T
BayesDel_noAF
Benign
-0.52
CADD
Uncertain
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.18
.;.;T;.;T
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.89
.;D;D;D;D
M_CAP
Benign
0.029
D
MetaRNN
Benign
0.22
T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.1
M;.;M;M;.
MutationTaster
Benign
0.96
D;D;D;D;D
PrimateAI
Benign
0.47
T
PROVEAN
Benign
-0.91
N;N;N;N;N
REVEL
Benign
0.15
Sift
Uncertain
0.0020
D;D;D;D;D
Sift4G
Benign
0.25
T;T;T;T;.
Polyphen
1.0
D;D;D;D;.
Vest4
0.57
MutPred
0.057
Gain of methylation at K1098 (P = 0.1612);.;Gain of methylation at K1098 (P = 0.1612);Gain of methylation at K1098 (P = 0.1612);Gain of methylation at K1098 (P = 0.1612);
MVP
0.45
MPC
0.41
ClinPred
0.78
D
GERP RS
5.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.20
gMVP
0.20

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: chrX-39923814; API