X-103063024-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_018476.4(BEX1):​c.251G>A​(p.Arg84Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000926 in 1,209,322 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 36 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 (★).

Frequency

Genomes: 𝑓 0.00049 ( 0 hom., 18 hem., cov: 22)
Exomes 𝑓: 0.000053 ( 0 hom. 18 hem. )

Consequence

BEX1
NM_018476.4 missense

Scores

1
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.256
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 Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0068727136).
BS2
High Hemizygotes in GnomAd4 at 18 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
BEX1NM_018476.4 linkc.251G>A p.Arg84Lys missense_variant Exon 3 of 3 ENST00000372728.4 NP_060946.3 Q9HBH7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
BEX1ENST00000372728.4 linkc.251G>A p.Arg84Lys missense_variant Exon 3 of 3 1 NM_018476.4 ENSP00000361813.3 Q9HBH7

Frequencies

GnomAD3 genomes
AF:
0.000486
AC:
54
AN:
111003
Hom.:
0
Cov.:
22
AF XY:
0.000543
AC XY:
18
AN XY:
33167
show subpopulations
Gnomad AFR
AF:
0.00177
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:
0.000153
AC:
28
AN:
183532
Hom.:
0
AF XY:
0.000118
AC XY:
8
AN XY:
67960
show subpopulations
Gnomad AFR exome
AF:
0.00213
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:
0.0000528
AC:
58
AN:
1098265
Hom.:
0
Cov.:
31
AF XY:
0.0000495
AC XY:
18
AN XY:
363619
show subpopulations
Gnomad4 AFR exome
AF:
0.00178
Gnomad4 AMR exome
AF:
0.000170
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:
0.00000237
Gnomad4 OTH exome
AF:
0.0000651
GnomAD4 genome
AF:
0.000486
AC:
54
AN:
111057
Hom.:
0
Cov.:
22
AF XY:
0.000542
AC XY:
18
AN XY:
33231
show subpopulations
Gnomad4 AFR
AF:
0.00177
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
Alfa
AF:
0.0000600
Hom.:
0
Bravo
AF:
0.000567
ESP6500AA
AF:
0.00183
AC:
7
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.000189
AC:
23

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Dec 17, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.251G>A (p.R84K) alteration is located in exon 3 (coding exon 1) of the BEX1 gene. This alteration results from a G to A substitution at nucleotide position 251, causing the arginine (R) at amino acid position 84 to be replaced by a lysine (K). 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
0.12
BayesDel_addAF
Benign
-0.68
T
BayesDel_noAF
Benign
-0.76
CADD
Benign
17
DANN
Benign
0.97
DEOGEN2
Benign
0.20
T
FATHMM_MKL
Benign
0.00070
N
LIST_S2
Benign
0.66
T
M_CAP
Benign
0.032
D
MetaRNN
Benign
0.0069
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.6
M
PrimateAI
Benign
0.41
T
PROVEAN
Benign
-1.4
N
REVEL
Benign
0.12
Sift
Benign
0.28
T
Sift4G
Benign
0.59
T
Polyphen
0.026
B
Vest4
0.28
MVP
0.13
MPC
0.12
ClinPred
0.027
T
GERP RS
1.4
Varity_R
0.10
gMVP
0.43

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: rs141464074; hg19: chrX-102317952; API