chrX-40052320-T-C

Variant names:

• chrX-40052320-T-C
• NM_001123385.2:c.5057A>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001123385.2(BCOR):​c.5057A>G​(p.Asn1686Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: BCOR NM_001123385.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.84

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3010937).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCOR	NM_001123385.2	c.5057A>G	p.Asn1686Ser	missense_variant	Exon 15 of 15	ENST00000378444.9	NP_001116857.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCOR	ENST00000378444.9	c.5057A>G	p.Asn1686Ser	missense_variant	Exon 15 of 15	1	NM_001123385.2	ENSP00000367705.4

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Oct 17, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.5057A>G (p.N1686S) alteration is located in exon 15 (coding exon 14) of the BCOR gene. This alteration results from a A to G substitution at nucleotide position 5057, causing the asparagine (N) at amino acid position 1686 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.038	.;T;.;.;T;.
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.86	D;D;.;D;D;D
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.30	T;T;T;T;T;T
MetaSVM	Benign	-0.73	T
MutationAssessor	Benign	1.1	.;.;.;.;L;.
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-2.6	D;D;N;N;N;N
REVEL	Benign	0.11
Sift	Benign	0.056	T;T;T;T;T;T
Sift4G	Benign	0.067	T;T;T;T;T;T
Polyphen		0.063, 0.21	.;.;B;B;B;B
Vest4		0.22, 0.21, 0.13, 0.14, 0.23
MutPred		0.72		.;.;.;.;Gain of MoRF binding (P = 0.1483);.;
MVP		0.57
MPC		0.82
ClinPred		0.40	T
GERP RS		4.3
Varity_R		0.13
gMVP		0.12

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-39911573; COSMIC: COSV60721150;