X-130005295-A-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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 (★).

• 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

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCORL1	NM_001379451.1	c.64A>G	p.Met22Val	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.64A>G	p.Met22Val	missense_variant	Exon 2 of 14	1	NM_001379451.1	ENSP00000437775.2
BCORL1	ENST00000218147.11	c.64A>G	p.Met22Val	missense_variant	Exon 2 of 13	5		ENSP00000218147.7
BCORL1	ENST00000607874.1	c.64A>G	p.Met22Val	missense_variant	Exon 3 of 3	3		ENSP00000484149.1
BCORL1	ENST00000488135.6	n.64A>G		non_coding_transcript_exon_variant	Exon 3 of 6	3		ENSP00000476643.1

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000119

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 28, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.64A>G (p.M22V) alteration is located in exon 1 (coding exon 1) of the BCORL1 gene. This alteration results from a A to G substitution at nucleotide position 64, causing the methionine (M) at amino acid position 22 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;T;T
MetaSVM	Benign	-0.39	T
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-2.1	.;N;N
REVEL	Benign	0.28
Sift	Uncertain	0.0020	.;D;D
Sift4G	Pathogenic	0.0	D;D;D
Vest4		0.77, 0.68
MutPred		0.25		Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);
MVP		0.92
MPC		0.42
ClinPred		0.89	D
GERP RS		4.7
gMVP		0.42

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

Publications

LitVar

Other links and lift over

dbSNP: rs1928397980; hg19: chrX-129139271;