rs587778099

Positions:

• chrX-40075041-C-A
• chrX-40075041-C-G
• chrX-40075041-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000378444.9(BCOR):​c.305G>T​(p.Arg102Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. R102P) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 22)
• Consequence: BCOR ENST00000378444.9 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.33

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCOR	NM_001123385.2	c.305G>T	p.Arg102Leu	missense_variant	4/15	ENST00000378444.9	NP_001116857.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BCOR	ENST00000378444.9	c.305G>T	p.Arg102Leu	missense_variant	4/15	1	NM_001123385.2	ENSP00000367705	P2

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.52	.;.;D;.;T
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.91	.;D;D;D;D
M_CAP	Uncertain	0.19	D
MetaRNN	Uncertain	0.70	D;D;D;D;D
MetaSVM	Uncertain	-0.21	T
MutationAssessor	Benign	1.7	L;L;L;L;.
MutationTaster	Benign	0.99	D;D;D;D
PrimateAI	Uncertain	0.68	T
PROVEAN	Uncertain	-3.1	D;D;D;D;D
REVEL	Uncertain	0.47
Sift	Uncertain	0.0010	D;D;D;D;D
Sift4G	Uncertain	0.026	D;D;D;D;.
Polyphen		1.0	D;D;D;D;.
Vest4		0.81
MutPred		0.39		Gain of helix (P = 0.0425);Gain of helix (P = 0.0425);Gain of helix (P = 0.0425);Gain of helix (P = 0.0425);Gain of helix (P = 0.0425);
MVP		0.79
MPC		0.90
ClinPred		0.96	D
GERP RS		5.3
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.7
Varity_R		0.40
gMVP		0.69

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.

Other links and lift over

hg19: chrX-39934294; COSMIC: COSV100654262; COSMIC: COSV100654262;