X-102154079-C-T

Variant summary

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

The NM_001012978.3(BEX5):​c.187G>A​(p.Gly63Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 20)

Consequence

BEX5
NM_001012978.3 missense

Scores

3
1
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.968
Variant links:
Genes affected
BEX5 (HGNC:27990): (brain expressed X-linked 5) Predicted to enable signaling receptor binding activity. Predicted to be involved in signal transduction. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

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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=0.38210577).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
BEX5NM_001012978.3 linkc.187G>A p.Gly63Arg missense_variant Exon 3 of 3 ENST00000333643.4 NP_001012996.1 Q5H9J7
BEX5NM_001159560.2 linkc.187G>A p.Gly63Arg missense_variant Exon 3 of 3 NP_001153032.1 Q5H9J7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
BEX5ENST00000333643.4 linkc.187G>A p.Gly63Arg missense_variant Exon 3 of 3 1 NM_001012978.3 ENSP00000328030.3 Q5H9J7
BEX5ENST00000543160.5 linkc.187G>A p.Gly63Arg missense_variant Exon 3 of 3 3 ENSP00000446054.1 Q5H9J7

Frequencies

GnomAD3 genomes
Cov.:
20
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
20

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 09, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.187G>A (p.G63R) alteration is located in exon 3 (coding exon 1) of the BEX5 gene. This alteration results from a G to A substitution at nucleotide position 187, causing the glycine (G) at amino acid position 63 to be replaced by an arginine (R). 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
Pathogenic
0.57
BayesDel_addAF
Benign
-0.066
T
BayesDel_noAF
Benign
-0.33
CADD
Benign
21
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.015
T;T
FATHMM_MKL
Benign
0.39
N
LIST_S2
Benign
0.82
T;.
M_CAP
Benign
0.0023
T
MetaRNN
Benign
0.38
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.6
M;M
PrimateAI
Pathogenic
0.86
D
PROVEAN
Benign
0.31
N;N
REVEL
Benign
0.17
Sift
Benign
0.29
T;T
Sift4G
Benign
0.59
T;T
Polyphen
1.0
D;D
Vest4
0.35
MutPred
0.40
Gain of solvent accessibility (P = 0.0097);Gain of solvent accessibility (P = 0.0097);
MVP
0.75
MPC
0.94
ClinPred
0.76
D
GERP RS
4.0
Varity_R
0.21
gMVP
0.080

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-101409051; API