chrX-40052325-A-C

Position:

• chrX-40052325-A-C

Variant summary

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

The NM_001123385.2(BCOR):​c.5052T>G​(p.Phe1684Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000911 in 1,098,005 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: BCOR NM_001123385.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.23

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	UniProt
BCOR	NM_001123385.2	c.5052T>G	p.Phe1684Leu	missense_variant	15/15	ENST00000378444.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCOR	ENST00000378444.9	c.5052T>G	p.Phe1684Leu	missense_variant	15/15	1	NM_001123385.2	P2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 9.11e-7 AC: 1 AN: 1098005 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 363359

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.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2024

BCOR: PM2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	.;T;.;.;D;.
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.91	D;D;.;D;D;D
M_CAP	Benign	0.033	D
MetaRNN	Uncertain	0.55	D;D;D;D;D;D
MetaSVM	Benign	-0.35	T
MutationAssessor	Uncertain	2.5	.;.;.;.;M;.
MutationTaster	Benign	0.99	D;D;D;D;D
PrimateAI	Uncertain	0.73	T
PROVEAN	Pathogenic	-5.3	D;D;D;D;D;D
REVEL	Benign	0.28
Sift	Benign	0.041	D;D;D;D;D;D
Sift4G	Uncertain	0.010	D;D;D;D;D;D
Polyphen		0.76, 0.21	.;.;P;P;B;P
Vest4		0.78, 0.50, 0.49, 0.48, 0.58
MutPred		0.49		.;.;.;.;Gain of catalytic residue at F1684 (P = 0.0107);.;
MVP		0.95
MPC		0.39
ClinPred		0.97	D
GERP RS		0.96
Varity_R		0.70
gMVP		0.70

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-39911578; COSMIC: COSV60706428;