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GeneBe

X-103063225-G-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_018476.4(BEX1):c.50C>A(p.Ala17Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,209,237 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. 13/20 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. A17V) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 1 hem., cov: 22)
Exomes 𝑓: 0.0000027 ( 0 hom. 1 hem. )

Consequence

BEX1
NM_018476.4 missense

Scores

1
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.159
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.042336047).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
BEX1NM_018476.4 linkuse as main transcriptc.50C>A p.Ala17Asp missense_variant 3/3 ENST00000372728.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
BEX1ENST00000372728.4 linkuse as main transcriptc.50C>A p.Ala17Asp missense_variant 3/31 NM_018476.4 P1

Frequencies

GnomAD3 genomes
AF:
0.0000270
AC:
3
AN:
111234
Hom.:
0
Cov.:
22
AF XY:
0.0000299
AC XY:
1
AN XY:
33450
show subpopulations
Gnomad AFR
AF:
0.0000982
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:
0.0000164
AC:
3
AN:
182447
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
67241
show subpopulations
Gnomad AFR exome
AF:
0.000229
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:
0.00000273
AC:
3
AN:
1098003
Hom.:
0
Cov.:
31
AF XY:
0.00000275
AC XY:
1
AN XY:
363359
show subpopulations
Gnomad4 AFR exome
AF:
0.000114
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:
0.0000270
AC:
3
AN:
111234
Hom.:
0
Cov.:
22
AF XY:
0.0000299
AC XY:
1
AN XY:
33450
show subpopulations
Gnomad4 AFR
AF:
0.0000982
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:
0.0000340
ExAC
AF:
0.0000247
AC:
3

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 GeneticsSep 27, 2022The c.50C>A (p.A17D) alteration is located in exon 3 (coding exon 1) of the BEX1 gene. This alteration results from a C to A substitution at nucleotide position 50, causing the alanine (A) at amino acid position 17 to be replaced by an aspartic acid (D). 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
0.10
BayesDel_addAF
Benign
-0.71
T
BayesDel_noAF
Benign
-0.96
Cadd
Benign
5.8
Dann
Benign
0.84
DEOGEN2
Benign
0.25
T
FATHMM_MKL
Benign
0.00038
N
LIST_S2
Benign
0.16
T
M_CAP
Benign
0.021
T
MetaRNN
Benign
0.042
T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
1.2
L
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.43
T
PROVEAN
Uncertain
-2.6
D
REVEL
Benign
0.024
Sift
Benign
0.11
T
Sift4G
Benign
0.084
T
Polyphen
0.0
B
Vest4
0.14
MutPred
0.39
Gain of helix (P = 0.062);
MVP
0.068
MPC
0.10
ClinPred
0.010
T
GERP RS
0.015
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.36
gMVP
0.31

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: rs1045065; hg19: chrX-102318153; API