X-130005259-G-C

Variant names:

• chrX-130005259-G-C
• rs1325772447
• NM_001379451.1:c.28G>C

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.28G>C​(p.Gly10Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000911 in 1,097,970 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. 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. G10S) 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: Not reported in ClinVar
• Conservation: PhyloP100: 2.83
• 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=0.23121873).

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.28G>C	p.Gly10Arg	missense	Exon 2 of 14	NP_001366380.1	Q5H9F3-3
	BCORL1	NM_001184772.3		c.28G>C	p.Gly10Arg	missense	Exon 3 of 15	NP_001171701.1	Q5H9F3-3
	BCORL1	NM_001379450.1		c.28G>C	p.Gly10Arg	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.28G>C	p.Gly10Arg	missense	Exon 2 of 14	ENSP00000437775.2	Q5H9F3-3
	BCORL1	ENST00000218147.11	TSL:5	c.28G>C	p.Gly10Arg	missense	Exon 2 of 13	ENSP00000218147.7	Q5H9F3-1
	BCORL1	ENST00000607874.1	TSL:3	c.28G>C	p.Gly10Arg	missense	Exon 3 of 3	ENSP00000484149.1	A0A087X1F0

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 9.11e-7 AC: 1 AN: 1097970 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 363344

African (AFR) AF: 0.00 AC: 0 AN: 26399

American (AMR) AF: 0.00 AC: 0 AN: 35195

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 30195

South Asian (SAS) AF: 0.00 AC: 0 AN: 54108

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40516

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4136

European-Non Finnish (NFE) AF: 0.00000119 AC: 1 AN: 841963

Other (OTH) AF: 0.00 AC: 0 AN: 46076

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.83
BayesDel_addAF	Benign	-0.015	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	18
DANN	Uncertain	1.0
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.059	D
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.81	T
PhyloP100		2.8
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.18
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0	D
Vest4		0.52
MutPred		0.31		Gain of MoRF binding (P = 0.0055)
MVP		0.64
MPC		0.50
ClinPred		0.73	D
GERP RS		3.9
gMVP		0.54
Mutation Taster		=79/21	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: rs1325772447; hg19: chrX-129139235;