X-40072699-C-T

Position:

• chrX-40072699-C-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP6

The NM_001123385.2(BCOR):​c.2647G>A​(p.Val883Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency: Genomes: not found (cov: 23)
• Consequence: BCOR NM_001123385.2 missense
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: -0.420

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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.044321716).
• BP6: Variant X-40072699-C-T is Benign according to our data. Variant chrX-40072699-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 411860.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCOR	NM_001123385.2	c.2647G>A	p.Val883Ile	missense_variant	4/15	ENST00000378444.9	NP_001116857.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BCOR	ENST00000378444.9	c.2647G>A	p.Val883Ile	missense_variant	4/15	1	NM_001123385.2	ENSP00000367705	P2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 23

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:1

Revision: criteria provided, conflicting classifications

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 11, 2017

- -

Oculofaciocardiodental syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jun 24, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.4
DANN	Benign	0.75
DEOGEN2	Benign	0.094	.;.;T;.;T;.
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.77	.;T;T;T;T;T
M_CAP	Benign	0.083	D
MetaRNN	Benign	0.044	T;T;T;T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.49	N;N;N;N;.;.
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.020	N;N;N;N;N;.
REVEL	Benign	0.023
Sift	Benign	0.45	T;T;T;T;T;.
Sift4G	Benign	0.31	T;T;T;T;.;T
Polyphen		0.0010	B;B;B;B;.;.
Vest4		0.030
MutPred		0.28		Gain of helix (P = 0.005);Gain of helix (P = 0.005);Gain of helix (P = 0.005);Gain of helix (P = 0.005);Gain of helix (P = 0.005);.;
MVP		0.19
MPC		0.21
ClinPred		0.033	T
GERP RS		1.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.040
gMVP		0.065

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: rs909942650; hg19: chrX-39931952;