Menu
GeneBe

X-103063180-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_018476.4(BEX1):c.95A>G(p.Glu32Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000827 in 1,209,631 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 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 0.000054 ( 0 hom., 1 hem., cov: 22)
Exomes 𝑓: 0.0000036 ( 0 hom. 1 hem. )

Consequence

BEX1
NM_018476.4 missense

Scores

4
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.652
Variant links:
Genes affected
BEX1 (HGNC:1036): (brain expressed X-linked 1) Enables RNA polymerase II-specific DNA-binding transcription factor binding activity. Involved in positive regulation of DNA-binding transcription factor activity and positive regulation of transcription by RNA polymerase II. Part of transcription regulator complex. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.22400558).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
BEX1NM_018476.4 linkuse as main transcriptc.95A>G p.Glu32Gly missense_variant 3/3 ENST00000372728.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
BEX1ENST00000372728.4 linkuse as main transcriptc.95A>G p.Glu32Gly missense_variant 3/31 NM_018476.4 P1

Frequencies

GnomAD3 genomes
AF:
0.0000538
AC:
6
AN:
111439
Hom.:
0
Cov.:
22
AF XY:
0.0000297
AC XY:
1
AN XY:
33621
show subpopulations
Gnomad AFR
AF:
0.000196
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
GnomAD3 exomes
AF:
0.0000109
AC:
2
AN:
183158
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
67662
show subpopulations
Gnomad AFR exome
AF:
0.000152
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000364
AC:
4
AN:
1098192
Hom.:
0
Cov.:
31
AF XY:
0.00000275
AC XY:
1
AN XY:
363546
show subpopulations
Gnomad4 AFR exome
AF:
0.000152
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:
0.00
GnomAD4 genome
AF:
0.0000538
AC:
6
AN:
111439
Hom.:
0
Cov.:
22
AF XY:
0.0000297
AC XY:
1
AN XY:
33621
show subpopulations
Gnomad4 AFR
AF:
0.000196
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:
0.0000529

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsFeb 22, 2023The c.95A>G (p.E32G) alteration is located in exon 3 (coding exon 1) of the BEX1 gene. This alteration results from a A to G substitution at nucleotide position 95, causing the glutamic acid (E) at amino acid position 32 to be replaced by a glycine (G). 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
Benign
0.14
BayesDel_addAF
Benign
-0.46
T
BayesDel_noAF
Benign
-0.65
Cadd
Benign
19
Dann
Uncertain
1.0
DEOGEN2
Benign
0.29
T
FATHMM_MKL
Benign
0.0012
N
LIST_S2
Benign
0.79
T
M_CAP
Benign
0.0064
T
MetaRNN
Benign
0.22
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.6
M
MutationTaster
Benign
1.0
N
PrimateAI
Uncertain
0.50
T
PROVEAN
Uncertain
-3.9
D
REVEL
Benign
0.12
Sift
Benign
0.17
T
Sift4G
Benign
0.12
T
Polyphen
0.86
P
Vest4
0.21
MVP
0.22
MPC
0.31
ClinPred
0.78
D
GERP RS
3.3
Varity_R
0.15
gMVP
0.32

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: rs894726025; hg19: chrX-102318108; API