X-130005295-A-G

Variant names:

• chrX-130005295-A-G
• rs1928397980
• NM_001379451.1:c.64A>G

Variant summary

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

The NM_001379451.1(BCORL1):​c.64A>G​(p.Met22Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000911 in 1,097,925 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M22L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: BCORL1 NM_001379451.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.64
• 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 2 ACMG points.

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

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.64A>G	p.Met22Val	missense	Exon 2 of 14	NP_001366380.1	Q5H9F3-3
	BCORL1	NM_001184772.3		c.64A>G	p.Met22Val	missense	Exon 3 of 15	NP_001171701.1	Q5H9F3-3
	BCORL1	NM_001379450.1		c.64A>G	p.Met22Val	missense	Exon 2 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.64A>G	p.Met22Val	missense	Exon 2 of 14	ENSP00000437775.2	Q5H9F3-3
	BCORL1	ENST00000218147.11	TSL:5	c.64A>G	p.Met22Val	missense	Exon 2 of 13	ENSP00000218147.7	Q5H9F3-1
	BCORL1	ENST00000607874.1	TSL:3	c.64A>G	p.Met22Val	missense	Exon 3 of 3	ENSP00000484149.1	A0A087X1F0

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 9.11e-7 AC: 1 AN: 1097925 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 363299

African (AFR) AF: 0.00 AC: 0 AN: 26394

American (AMR) AF: 0.00 AC: 0 AN: 35204

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19376

East Asian (EAS) AF: 0.00 AC: 0 AN: 30202

South Asian (SAS) AF: 0.00 AC: 0 AN: 54122

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40519

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4135

European-Non Finnish (NFE) AF: 0.00000119 AC: 1 AN: 841893

Other (OTH) AF: 0.00 AC: 0 AN: 46080

GnomAD4 genome Cov.: 23

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.51
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Benign	22
DANN	Uncertain	0.99
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.050	D
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-0.39	T
PhyloP100		6.6
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.28
Sift	Uncertain	0.0020	D
Sift4G	Pathogenic	0.0	D
Vest4		0.77
MutPred		0.25		Loss of helix (P = 0.0558)
MVP		0.92
MPC		0.42
ClinPred		0.89	D
GERP RS		4.7
gMVP		0.42
Mutation Taster		=83/17	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1928397980; hg19: chrX-129139271;