X-130012586-C-T

Variant names:

• chrX-130012586-C-T
• rs1603105985
• NM_001379451.1:c.95C>T

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PP3 PP5_Moderate

The NM_001379451.1(BCORL1):​c.95C>T​(p.Pro32Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency: Genomes: not found (cov: 24)
• Consequence: BCORL1 NM_001379451.1 missense
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:2
• Conservation: PhyloP100: 5.10

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.79
• PP5: Variant X-130012586-C-T is Pathogenic according to our data. Variant chrX-130012586-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 638170.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCORL1	NM_001379451.1	c.95C>T	p.Pro32Leu	missense_variant	Exon 3 of 14	ENST00000540052.6	NP_001366380.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCORL1	ENST00000540052.6	c.95C>T	p.Pro32Leu	missense_variant	Exon 3 of 14	1	NM_001379451.1	ENSP00000437775.2
BCORL1	ENST00000218147.11	c.95C>T	p.Pro32Leu	missense_variant	Exon 3 of 13	5		ENSP00000218147.7
BCORL1	ENST00000488135.6	n.*113C>T		non_coding_transcript_exon_variant	Exon 5 of 6	3		ENSP00000476643.1
BCORL1	ENST00000488135.6	n.*113C>T		3_prime_UTR_variant	Exon 5 of 6	3		ENSP00000476643.1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 24

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, single submitter

Submissions by phenotype

Shukla-Vernon syndrome Pathogenic:2

-

Kasturba Medical College, Manipal, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: research

- -

Jul 25, 2019

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Uncertain	0.029	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	24
DANN	Uncertain	0.99
FATHMM_MKL	Pathogenic	0.99	D
M_CAP	Pathogenic	0.67	D
MetaRNN	Pathogenic	0.79	D;D
MetaSVM	Benign	-0.80	T
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-3.6	D;D
REVEL	Benign	0.23
Sift	Uncertain	0.0010	D;D
Sift4G	Uncertain	0.0040	D;D
Vest4		0.73
MutPred		0.32		Loss of loop (P = 0.0389);Loss of loop (P = 0.0389);
MVP		0.61
MPC		0.42
ClinPred		0.96	D
GERP RS		5.4
gMVP		0.43

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: rs1603105985; hg19: chrX-129146562;