Genetic Variant BEX5:p.Asp56Gly (chrX-102154099-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001012978.3(BEX5):c.167A>G(p.Asp56Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000108 in 1,207,335 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000092 ( 0 hom., 0 hem., cov: 20)

Exomes 𝑓: 0.000011 ( 0 hom. 1 hem. )

Consequence

BEX5
NM_001012978.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.22

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]

BEX5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.21483472).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BEX5	NM_001012978.3 link	c.167A>G	p.Asp56Gly	missense_variant	Exon 3 of 3	ENST00000333643.4	NP_001012996.1	Q5H9J7
BEX5	NM_001159560.2 link	c.167A>G	p.Asp56Gly	missense_variant	Exon 3 of 3		NP_001153032.1	Q5H9J7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BEX5	ENST00000333643.4 link	c.167A>G	p.Asp56Gly	missense_variant	Exon 3 of 3	1	NM_001012978.3	ENSP00000328030.3		Q5H9J7
BEX5	ENST00000543160.5 link	c.167A>G	p.Asp56Gly	missense_variant	Exon 3 of 3	3		ENSP00000446054.1		Q5H9J7

Frequencies

GnomAD3 genomes

AF:

0.00000917

AC:

AN:

109080

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

31344

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000190

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000545

AC:

AN:

183506

Hom.:

AF XY:

0.00

AC XY:

AN XY:

67938

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000365

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:

0.0000109

AC:

AN:

1098255

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

363609

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000284

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:

0.0000107

Gnomad4 OTH exome

AF:

0.0000217

GnomAD4 genome

AF:

0.00000917

AC:

AN:

109080

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

31344

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000190

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 16, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.167A>G (p.D56G) alteration is located in exon 3 (coding exon 1) of the BEX5 gene. This alteration results from a A to G substitution at nucleotide position 167, causing the aspartic acid (D) at amino acid position 56 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

0.13

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.024

T;T

FATHMM_MKL

Benign

0.45

LIST_S2

Benign

0.50

T;.

M_CAP

Benign

0.0042

MetaRNN

Benign

0.21

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

L;L

PrimateAI

Uncertain

0.68

PROVEAN

Uncertain

-2.5

D;D

REVEL

Benign

0.15

Sift

Benign

0.049

D;D

Sift4G

Benign

0.44

T;T

Polyphen

0.19

B;B

Vest4

0.16

MutPred

0.55

Loss of stability (P = 0.028);Loss of stability (P = 0.028);

MVP

0.51

MPC

0.37

ClinPred

0.19

GERP RS

4.0

Varity_R

0.32

gMVP

0.070

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over