Genetic Variant NM_001379451.1:c.310A>C (chrX-130013082-A-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001379451.1(BCORL1):c.310A>C(p.Asn104His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000912 in 1,096,887 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. 12/18 in silico tools predict a benign outcome for this variant. 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

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.31

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]

BCORL1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19664574).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCORL1	NM_001379451.1 link	c.310A>C	p.Asn104His	missense_variant	Exon 4 of 14	ENST00000540052.6	NP_001366380.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
BCORL1	ENST00000540052.6 link	c.310A>C	p.Asn104His	missense_variant	Exon 4 of 14	1	NM_001379451.1	ENSP00000437775.2	Q5H9F3-3
BCORL1	ENST00000218147.11 link	c.310A>C	p.Asn104His	missense_variant	Exon 4 of 13	5		ENSP00000218147.7	Q5H9F3-1
BCORL1	ENST00000488135.6 link	n.*328A>C		non_coding_transcript_exon_variant	Exon 6 of 6	3		ENSP00000476643.1	V9GYD4
BCORL1	ENST00000488135.6 link	n.*328A>C		3_prime_UTR_variant	Exon 6 of 6	3		ENSP00000476643.1	V9GYD4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

9.12e-7

AC:

AN:

1096887

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

362367

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:

0.00000119

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Apr 30, 2024

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 indicates 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

0.10

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.80

CADD

Benign

DANN

Uncertain

0.98

FATHMM_MKL

Uncertain

0.81

M_CAP

Benign

0.026

MetaRNN

Benign

0.20

T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.73

N;N

REVEL

Benign

0.035

Sift

Uncertain

0.0090

D;D

Sift4G

Uncertain

0.031

D;D

Vest4

0.088

MutPred

0.26

Loss of loop (P = 0.0075);Loss of loop (P = 0.0075);

MVP

0.48

MPC

0.43

ClinPred

0.33

GERP RS

3.7

gMVP

0.14

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over