X-130005257-G-A

Variant names:

• chrX-130005257-G-A
• rs1928393361
• NM_001379451.1:c.26G>A

Variant summary

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

The NM_001379451.1(BCORL1):​c.26G>A​(p.Ser9Asn) 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: BCORL1 NM_001379451.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.36

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34210926).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCORL1	NM_001379451.1	c.26G>A	p.Ser9Asn	missense_variant	Exon 2 of 14	ENST00000540052.6	NP_001366380.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCORL1	ENST00000540052.6	c.26G>A	p.Ser9Asn	missense_variant	Exon 2 of 14	1	NM_001379451.1	ENSP00000437775.2
BCORL1	ENST00000218147.11	c.26G>A	p.Ser9Asn	missense_variant	Exon 2 of 13	5		ENSP00000218147.7
BCORL1	ENST00000607874.1	c.26G>A	p.Ser9Asn	missense_variant	Exon 3 of 3	3		ENSP00000484149.1
BCORL1	ENST00000488135.6	n.26G>A		non_coding_transcript_exon_variant	Exon 3 of 6	3		ENSP00000476643.1

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

Shukla-Vernon syndrome Uncertain:1

Feb 09, 2021

Institute for Human Genetics and Genomic Medicine, Uniklinik RWTH Aachen

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The variant has not yet been reported in the relevant databases (dbSNP151, gnomAD, ClinVar) or in the literature. From a bioinformatics point of view, the change is classified as "likely disease causing" (PolyPhen2, Mutation Taster, SIFT). At this point in time, the variant is to be regarded as a "variant of uncertain clinical significance" (ACMG criteria). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	21
DANN	Uncertain	0.99
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.79	T;.;.
M_CAP	Benign	0.059	D
MetaRNN	Benign	0.34	T;T;T
MetaSVM	Benign	-0.47	T
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-0.74	.;N;N
REVEL	Benign	0.12
Sift	Uncertain	0.0010	.;D;D
Sift4G	Pathogenic	0.0	D;D;D
Vest4		0.58, 0.44
MutPred		0.14		Loss of glycosylation at S9 (P = 0.0429);Loss of glycosylation at S9 (P = 0.0429);Loss of glycosylation at S9 (P = 0.0429);
MVP		0.58
MPC		0.39
ClinPred		0.70	D
GERP RS		4.7
gMVP		0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1928393361; hg19: chrX-129139233;