X-40074260-GGC-TGT

Variant names:

• chrX-40074260-GGC-TGT
• NM_001123385.2:c.1084_1086delGCCinsACA
• BCOR p.Ala362Thr

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001123385.2(BCOR):​c.1084_1086delGCCinsACA​(p.Ala362Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 24)
• Consequence: BCOR NM_001123385.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.46
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• microphthalmia, syndromic 2

  Inheritance: XL, Unknown Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), Illumina, Orphanet, ClinGen, Ambry Genetics
• microphthalmia, Lenz type

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001123385.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCOR	NM_001123385.2	MANE Select	c.1084_1086delGCCinsACA	p.Ala362Thr	missense	N/A	NP_001116857.1	Q6W2J9-1
	BCOR	NM_001437510.1		c.1084_1086delGCCinsACA	p.Ala362Thr	missense	N/A	NP_001424439.1
	BCOR	NM_001438207.1		c.1084_1086delGCCinsACA	p.Ala362Thr	missense	N/A	NP_001425136.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCOR	ENST00000378444.9	TSL:1 MANE Select	c.1084_1086delGCCinsACA	p.Ala362Thr	missense	N/A	ENSP00000367705.4	Q6W2J9-1
	BCOR	ENST00000397354.7	TSL:1	c.1084_1086delGCCinsACA	p.Ala362Thr	missense	N/A	ENSP00000380512.3	Q6W2J9-2
	BCOR	ENST00000378455.8	TSL:1	c.1084_1086delGCCinsACA	p.Ala362Thr	missense	N/A	ENSP00000367716.4	Q6W2J9-4

Frequencies

GnomAD3 genomes Cov.: 24

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.5

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chrX-39933513;