X-40062856-C-T

Position:

• chrX-40062856-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001123385.2(BCOR):​c.4063G>A​(p.Glu1355Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000128 in 1,097,579 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 0.000013 (0 hom. 4 hem.)
• Consequence: BCOR NM_001123385.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.91

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 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High Hemizygotes in GnomAdExome4 at 4 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCOR	NM_001123385.2	c.4063G>A	p.Glu1355Lys	missense_variant	9/15	ENST00000378444.9	NP_001116857.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BCOR	ENST00000378444.9	c.4063G>A	p.Glu1355Lys	missense_variant	9/15	1	NM_001123385.2	ENSP00000367705.4

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD3 exomes AF: 0.0000165 AC: 3 AN: 181896 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 66414

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000145

Gnomad SAS exome AF: 0.0000535

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000128 AC: 14 AN: 1097579 Hom.: 0 Cov.: 32 AF XY: 0.0000110 AC XY: 4 AN XY: 362943

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000298

Gnomad4 SAS exome AF: 0.0000371

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000238

Gnomad4 OTH exome AF: 0.0000217

GnomAD4 genome Cov.: 22

Bravo AF: 0.0000113

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Pathogenic	0.18
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.041	.;T;.;.;T;.;T
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.93	D;D;.;D;D;D;D
M_CAP	Pathogenic	0.81	D
MetaRNN	Uncertain	0.56	D;D;D;D;D;D;D
MetaSVM	Uncertain	-0.017	T
MutationAssessor	Benign	2.0	.;.;.;.;M;.;.
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-3.2	D;D;D;D;D;D;D
REVEL	Uncertain	0.30
Sift	Uncertain	0.0010	D;D;D;D;D;D;D
Sift4G	Uncertain	0.037	D;D;D;T;T;D;D
Polyphen		1.0, 1.0	.;.;D;D;D;D;.
Vest4		0.47, 0.78, 0.78, 0.75, 0.72
MutPred		0.32		.;.;.;.;Gain of MoRF binding (P = 0.0039);.;.;
MVP		0.84
MPC		0.99
ClinPred		0.69	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.65
gMVP		0.34

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

Other links and lift over

dbSNP: rs780712297; hg19: chrX-39922109; COSMIC: COSV105904546; COSMIC: COSV105904546;