X-130013056-C-T

Variant names:

• chrX-130013056-C-T
• rs2124438652
• NM_001379451.1:c.284C>T

Variant summary

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

The NM_001379451.1(BCORL1):​c.284C>T​(p.Pro95Leu) 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. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 24)
• Consequence: BCORL1 NM_001379451.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.59
• Publications: 0 publications found

Genes affected

BCORL1 (HGNC:25657): (BCL6 corepressor like 1) The protein encoded by this gene is a transcriptional corepressor that is found tethered to promoter regions by DNA-binding proteins. The encoded protein can interact with several different class II histone deacetylases to repress transcription. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2010]

BCORL1 Gene-Disease associations (from GenCC):

• Shukla-Vernon syndrome

  Inheritance: XL Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Illumina, G2P, ClinGen, Labcorp Genetics (formerly Invitae)
• syndromic intellectual disability

  Inheritance: AD 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=0.07176027).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001379451.1. 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
	BCORL1	NM_001379451.1	MANE Select	c.284C>T	p.Pro95Leu	missense	Exon 4 of 14	NP_001366380.1	Q5H9F3-3
	BCORL1	NM_001184772.3		c.284C>T	p.Pro95Leu	missense	Exon 5 of 15	NP_001171701.1	Q5H9F3-3
	BCORL1	NM_001379450.1		c.284C>T	p.Pro95Leu	missense	Exon 4 of 14	NP_001366379.1	Q5H9F3-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCORL1	ENST00000540052.6	TSL:1 MANE Select	c.284C>T	p.Pro95Leu	missense	Exon 4 of 14	ENSP00000437775.2	Q5H9F3-3
	BCORL1	ENST00000218147.11	TSL:5	c.284C>T	p.Pro95Leu	missense	Exon 4 of 13	ENSP00000218147.7	Q5H9F3-1
	BCORL1	ENST00000488135.6	TSL:3	n.*302C>T		non_coding_transcript_exon	Exon 6 of 6	ENSP00000476643.1	V9GYD4

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 24

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	19
DANN	Uncertain	0.98
FATHMM_MKL	Benign	0.27	N
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.072	T
MetaSVM	Benign	-1.0	T
PhyloP100		1.6
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.64	N
REVEL	Benign	0.028
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.020	D
Vest4		0.11
MutPred		0.19		Loss of relative solvent accessibility (P = 0.0186)
MVP		0.16
MPC		0.42
ClinPred		0.18	T
GERP RS		2.4
gMVP		0.096
Mutation Taster		=89/11	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: rs2124438652; hg19: chrX-129147032;