X-40052319-G-T

Variant names:

• chrX-40052319-G-T
• rs369322807
• NM_001123385.2:c.5058C>A

Variant summary

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

The NM_001123385.2(BCOR):​c.5058C>A​(p.Asn1686Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000182 in 1,097,702 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. 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. N1686S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000018 (0 hom. 1 hem.)
• Consequence: BCOR NM_001123385.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0270

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCOR	NM_001123385.2	c.5058C>A	p.Asn1686Lys	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.5058C>A	p.Asn1686Lys	missense_variant	Exon 15 of 15	1	NM_001123385.2	ENSP00000367705.4

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000182 AC: 2 AN: 1097702 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 1 AN XY: 363062

African (AFR) AF: 0.00 AC: 0 AN: 26391

American (AMR) AF: 0.00 AC: 0 AN: 35206

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19382

East Asian (EAS) AF: 0.00 AC: 0 AN: 30204

South Asian (SAS) AF: 0.00 AC: 0 AN: 54133

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40533

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4134

European-Non Finnish (NFE) AF: 0.00000238 AC: 2 AN: 841648

Other (OTH) AF: 0.00 AC: 0 AN: 46071

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	7.4
DANN	Uncertain	0.99
DEOGEN2	Benign	0.074	.;T;.;.;T;.
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.84	T;T;.;T;T;T
M_CAP	Benign	0.033	D
MetaRNN	Uncertain	0.45	T;T;T;T;T;T
MetaSVM	Benign	-0.36	T
MutationAssessor	Benign	1.8	.;.;.;.;L;.
PhyloP100		0.027
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-3.0	D;D;D;D;D;D
REVEL	Benign	0.19
Sift	Uncertain	0.0050	D;D;D;D;D;D
Sift4G	Uncertain	0.019	D;D;D;D;D;D
Polyphen		0.93, 0.98	.;.;P;P;D;P
Vest4		0.35, 0.31, 0.27, 0.29, 0.44
MutPred		0.81		.;.;.;.;Gain of ubiquitination at N1686 (P = 0.0452);.;
MVP		0.50
MPC		1.0
ClinPred		0.93	D
GERP RS		-4.0
Varity_R		0.52
gMVP		0.26
Mutation Taster		=77/23	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

Publications

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Other links and lift over

dbSNP: rs369322807; hg19: chrX-39911572;