X-40072392-T-C

Variant names:

• chrX-40072392-T-C
• rs587778093
• NM_001123385.2:c.2954A>G

Variant summary

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

The NM_001123385.2(BCOR):​c.2954A>G​(p.Tyr985Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000638 in 1,096,484 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 5 hemizygotes in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.0000064 (0 hom. 5 hem.)
• Consequence: BCOR NM_001123385.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.87

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 Likely_benign. Variant got -4 ACMG points.

• BS2: High Hemizygotes in GnomAdExome4 at 5 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCOR	NM_001123385.2	c.2954A>G	p.Tyr985Cys	missense_variant	Exon 4 of 15	ENST00000378444.9	NP_001116857.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCOR	ENST00000378444.9	c.2954A>G	p.Tyr985Cys	missense_variant	Exon 4 of 15	1	NM_001123385.2	ENSP00000367705.4

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD3 exomes AF: 0.0000112 AC: 2 AN: 177824 Hom.: 0 AF XY: 0.0000159 AC XY: 1 AN XY: 62764

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000646

Gnomad NFE exome AF: 0.0000127

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000638 AC: 7 AN: 1096484 Hom.: 0 Cov.: 30 AF XY: 0.0000138 AC XY: 5 AN XY: 361940

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: 0.00000713

Gnomad4 OTH exome AF: 0.0000217

GnomAD4 genome Cov.: 24

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.030
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.69	.;.;D;.;T;.
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	0.97	.;D;D;D;D;D
M_CAP	Pathogenic	0.30	D
MetaRNN	Uncertain	0.47	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M;M;M;M;.;.
PrimateAI	Pathogenic	0.89	D
PROVEAN	Uncertain	-4.0	D;D;D;D;D;.
REVEL	Uncertain	0.29
Sift	Pathogenic	0.0	D;D;D;D;D;.
Sift4G	Uncertain	0.029	D;T;T;D;.;D
Polyphen		1.0	D;D;D;D;.;.
Vest4		0.86
MutPred		0.29		Loss of phosphorylation at Y985 (P = 0.026);Loss of phosphorylation at Y985 (P = 0.026);Loss of phosphorylation at Y985 (P = 0.026);Loss of phosphorylation at Y985 (P = 0.026);Loss of phosphorylation at Y985 (P = 0.026);.;
MVP		0.69
MPC		1.0
ClinPred		0.93	D
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.53
gMVP		0.84

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: rs587778093; hg19: chrX-39931645;