Menu
GeneBe

X-103063067-G-A

Variant summary

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

The NM_018476.4(BEX1):c.208C>T(p.Leu70Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000911 in 1,098,266 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. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 22)
Exomes 𝑓: 9.1e-7 ( 0 hom. 1 hem. )

Consequence

BEX1
NM_018476.4 missense

Scores

2
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.525
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 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=0.29697502).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
BEX1NM_018476.4 linkuse as main transcriptc.208C>T p.Leu70Phe missense_variant 3/3 ENST00000372728.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
BEX1ENST00000372728.4 linkuse as main transcriptc.208C>T p.Leu70Phe missense_variant 3/31 NM_018476.4 P1

Frequencies

GnomAD3 genomes
Cov.:
22
GnomAD4 exome
AF:
9.11e-7
AC:
1
AN:
1098266
Hom.:
0
Cov.:
31
AF XY:
0.00000275
AC XY:
1
AN XY:
363620
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
Cov.:
22

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 GeneticsJan 26, 2022The c.208C>T (p.L70F) alteration is located in exon 3 (coding exon 1) of the BEX1 gene. This alteration results from a C to T substitution at nucleotide position 208, causing the leucine (L) at amino acid position 70 to be replaced by a phenylalanine (F). 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
0.11
BayesDel_addAF
Benign
-0.28
T
BayesDel_noAF
Benign
-0.64
Cadd
Benign
19
Dann
Uncertain
1.0
DEOGEN2
Benign
0.29
T
FATHMM_MKL
Benign
0.0022
N
LIST_S2
Benign
0.67
T
M_CAP
Benign
0.051
D
MetaRNN
Benign
0.30
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.5
M
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.42
T
PROVEAN
Benign
-2.0
N
REVEL
Benign
0.10
Sift
Benign
0.040
D
Sift4G
Benign
0.092
T
Polyphen
0.99
D
Vest4
0.19
MutPred
0.31
Loss of catalytic residue at L70 (P = 0.0269);
MVP
0.22
MPC
0.13
ClinPred
0.56
D
GERP RS
1.1
Varity_R
0.13
gMVP
0.11

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-102317995; API