X-40062969-G-T

Variant names:

• chrX-40062969-G-T
• rs780412607
• NM_001123385.2:c.3950C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001123385.2(BCOR):​c.3950C>A​(p.Pro1317Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000093 in 1,075,116 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. 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. P1317L) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 9.3e-7 (0 hom. 0 hem.)
• Consequence: BCOR NM_001123385.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.100
• Publications: 1 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: Ambry Genetics, ClinGen, Illumina, Orphanet, Labcorp Genetics (formerly Invitae), G2P
• microphthalmia, Lenz type

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.088661045).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCOR	NM_001123385.2	MANE Select	c.3950C>A	p.Pro1317Gln	missense	Exon 9 of 15	NP_001116857.1
	BCOR	NM_001437510.1		c.3950C>A	p.Pro1317Gln	missense	Exon 9 of 15	NP_001424439.1
	BCOR	NM_001438207.1		c.3896C>A	p.Pro1299Gln	missense	Exon 8 of 14	NP_001425136.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCOR	ENST00000378444.9	TSL:1 MANE Select	c.3950C>A	p.Pro1317Gln	missense	Exon 9 of 15	ENSP00000367705.4
	BCOR	ENST00000397354.7	TSL:1	c.3848C>A	p.Pro1283Gln	missense	Exon 9 of 15	ENSP00000380512.3
	BCOR	ENST00000378455.8	TSL:1	c.3794C>A	p.Pro1265Gln	missense	Exon 8 of 14	ENSP00000367716.4

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 9.30e-7 AC: 1 AN: 1075116 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 349164

African (AFR) AF: 0.00 AC: 0 AN: 25923

American (AMR) AF: 0.00 AC: 0 AN: 31312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19079

East Asian (EAS) AF: 0.00 AC: 0 AN: 29155

South Asian (SAS) AF: 0.00 AC: 0 AN: 51481

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39087

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4100

European-Non Finnish (NFE) AF: 0.00000121 AC: 1 AN: 829757

Other (OTH) AF: 0.00 AC: 0 AN: 45222

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	16
DANN	Benign	0.94
DEOGEN2	Benign	0.015	T
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.74	T
M_CAP	Uncertain	0.20	D
MetaRNN	Benign	0.089	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.20	N
PhyloP100		0.10
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.11	N
REVEL	Benign	0.034
Sift	Benign	0.056	T
Sift4G	Benign	0.59	T
Polyphen		0.0020	B
Vest4		0.18
MutPred		0.28		Loss of glycosylation at P1317 (P = 0.0076)
MVP		0.54
MPC		0.25
ClinPred		0.073	T
GERP RS		-1.5
Varity_R		0.074
gMVP		0.13
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs780412607; hg19: chrX-39922222;