dbSNP rs782199206: BEX5:p.Arg70Leu (chrX-102154057-C-A) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_001012978.3(BEX5):c.209G>T(p.Arg70Leu) 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 1,098,075 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R70Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 20)

Exomes 𝑓: 9.1e-7 ( 0 hom. 0 hem. )

Consequence

BEX5
NM_001012978.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.458

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.755

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001012978.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BEX5	NM_001012978.3	MANE Select	c.209G>T	p.Arg70Leu	missense	Exon 3 of 3	NP_001012996.1	Q5H9J7
	BEX5	NM_001159560.2		c.209G>T	p.Arg70Leu	missense	Exon 3 of 3	NP_001153032.1	Q5H9J7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BEX5	ENST00000333643.4	TSL:1 MANE Select	c.209G>T	p.Arg70Leu	missense	Exon 3 of 3	ENSP00000328030.3	Q5H9J7
BEX5	ENST00000543160.5	TSL:3	c.209G>T	p.Arg70Leu	missense	Exon 3 of 3	ENSP00000446054.1	Q5H9J7
BEX5	ENST00000883041.1		c.209G>T	p.Arg70Leu	missense	Exon 2 of 2	ENSP00000553100.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

9.11e-7

AC:

AN:

1098075

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

363431

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26397

American (AMR)

AF:

0.00

AC:

AN:

35207

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19386

East Asian (EAS)

AF:

0.00

AC:

AN:

30205

South Asian (SAS)

AF:

0.00

AC:

AN:

54145

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40533

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4137

European-Non Finnish (NFE)

AF:

0.00000119

AC:

AN:

841971

Other (OTH)

AF:

0.00

AC:

AN:

46094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.020

BayesDel_noAF

Benign

-0.27

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.079

FATHMM_MKL

Benign

0.41

LIST_S2

Benign

0.41

M_CAP

Benign

0.010

MetaRNN

Pathogenic

0.76

MetaSVM

Benign

-1.0

MutationAssessor

Pathogenic

3.0

PhyloP100

0.46

PrimateAI

Pathogenic

0.79

PROVEAN

Pathogenic

-4.5

REVEL

Benign

0.18

Sift

Uncertain

0.011

Sift4G

Benign

0.28

Polyphen

0.96

Vest4

0.56

MutPred

0.77

Loss of MoRF binding (P = 0.0806)

MVP

0.76

MPC

0.78

ClinPred

0.98

GERP RS

3.1

Varity_R

0.30

gMVP

0.31

Mutation Taster

=90/10

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over