NM_001379451.1:c.64A>C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001379451.1(BCORL1):​c.64A>C​(p.Met22Leu) 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. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. 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. M22V) 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.40421686).

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>C	p.Met22Leu	missense	Exon 2 of 14	NP_001366380.1	Q5H9F3-3
	BCORL1	NM_001184772.3		c.64A>C	p.Met22Leu	missense	Exon 3 of 15	NP_001171701.1	Q5H9F3-3
	BCORL1	NM_001379450.1		c.64A>C	p.Met22Leu	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>C	p.Met22Leu	missense	Exon 2 of 14	ENSP00000437775.2	Q5H9F3-3
	BCORL1	ENST00000218147.11	TSL:5	c.64A>C	p.Met22Leu	missense	Exon 2 of 13	ENSP00000218147.7	Q5H9F3-1
	BCORL1	ENST00000607874.1	TSL:3	c.64A>C	p.Met22Leu	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

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	Uncertain	0.42
BayesDel_addAF	Uncertain	0.059	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	23
DANN	Benign	0.91
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.40	T
MetaSVM	Benign	-0.53	T
PhyloP100		6.6
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.29
Sift	Uncertain	0.010	D
Sift4G	Pathogenic	0.0	D
Vest4		0.71
MutPred		0.29		Loss of helix (P = 0.0558)
MVP		0.89
MPC		0.39
ClinPred		0.79	D
GERP RS		4.7
gMVP		0.30
Mutation Taster		=85/15	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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;