X-130012655-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001379451.1(BCORL1):​c.164G>A​(p.Ser55Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000165 in 1,208,957 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 0 hem., cov: 23)
Exomes 𝑓: 9.1e-7 ( 0 hom. 1 hem. )

Consequence

BCORL1
NM_001379451.1 missense

Scores

2
4
8

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 4.81
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.29293287).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
BCORL1NM_001379451.1 linkc.164G>A p.Ser55Asn missense_variant Exon 3 of 14 ENST00000540052.6 NP_001366380.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
BCORL1ENST00000540052.6 linkc.164G>A p.Ser55Asn missense_variant Exon 3 of 14 1 NM_001379451.1 ENSP00000437775.2 Q5H9F3-3
BCORL1ENST00000218147.11 linkc.164G>A p.Ser55Asn missense_variant Exon 3 of 13 5 ENSP00000218147.7 Q5H9F3-1
BCORL1ENST00000488135.6 linkn.*182G>A non_coding_transcript_exon_variant Exon 5 of 6 3 ENSP00000476643.1 V9GYD4
BCORL1ENST00000488135.6 linkn.*182G>A 3_prime_UTR_variant Exon 5 of 6 3 ENSP00000476643.1 V9GYD4

Frequencies

GnomAD3 genomes
AF:
0.00000890
AC:
1
AN:
112422
Hom.:
0
Cov.:
23
AF XY:
0.00
AC XY:
0
AN XY:
34560
show subpopulations
Gnomad AFR
AF:
0.0000323
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
9.12e-7
AC:
1
AN:
1096535
Hom.:
0
Cov.:
30
AF XY:
0.00000276
AC XY:
1
AN XY:
362025
show subpopulations
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:
0.00
Gnomad4 OTH exome
AF:
0.0000217
GnomAD4 genome
AF:
0.00000890
AC:
1
AN:
112422
Hom.:
0
Cov.:
23
AF XY:
0.00
AC XY:
0
AN XY:
34560
show subpopulations
Gnomad4 AFR
AF:
0.0000323
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Shukla-Vernon syndrome Uncertain:1
Jan 09, 2020
New York Genome Center
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

not provided Uncertain:1
Apr 14, 2023
GeneDx
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.23
BayesDel_addAF
Benign
-0.18
T
BayesDel_noAF
Benign
-0.50
CADD
Benign
21
DANN
Uncertain
0.98
FATHMM_MKL
Uncertain
0.95
D
M_CAP
Pathogenic
0.41
D
MetaRNN
Benign
0.29
T;T
MetaSVM
Benign
-1.0
T
PrimateAI
Uncertain
0.63
T
PROVEAN
Benign
-0.53
N;N
REVEL
Benign
0.046
Sift
Pathogenic
0.0
D;D
Sift4G
Uncertain
0.0020
D;D
Vest4
0.42
MutPred
0.23
Gain of catalytic residue at S55 (P = 0.0495);Gain of catalytic residue at S55 (P = 0.0495);
MVP
0.57
MPC
0.39
ClinPred
0.62
D
GERP RS
4.5
gMVP
0.30

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1179687241; hg19: chrX-129146631; API