X-102154122-C-G

Variant names:

• chrX-102154122-C-G
• rs946251881
• NM_001012978.3:c.144G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001012978.3(BEX5):​c.144G>C​(p.Glu48Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,207,901 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000036 (0 hom., 1 hem., cov: 20)
  • Exomes 𝑓: 0.0000091 (0 hom. 1 hem.)
• Consequence: BEX5 NM_001012978.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.438
• Publications: 1 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.18059856).

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.144G>C	p.Glu48Asp	missense	Exon 3 of 3	NP_001012996.1	Q5H9J7
	BEX5	NM_001159560.2		c.144G>C	p.Glu48Asp	missense	Exon 3 of 3	NP_001153032.1	Q5H9J7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BEX5	ENST00000333643.4	TSL:1 MANE Select	c.144G>C	p.Glu48Asp	missense	Exon 3 of 3	ENSP00000328030.3	Q5H9J7
	BEX5	ENST00000543160.5	TSL:3	c.144G>C	p.Glu48Asp	missense	Exon 3 of 3	ENSP00000446054.1	Q5H9J7
	BEX5	ENST00000883041.1		c.144G>C	p.Glu48Asp	missense	Exon 2 of 2	ENSP00000553100.1

Frequencies

GnomAD3 genomes AF: 0.0000365 AC: 4 AN: 109661 Hom.: 0 Cov.: 20

Gnomad AFR AF: 0.0000333

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000195

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

GnomAD2 exomes AF: 0.0000109 AC: 2 AN: 183519 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000729

Gnomad ASJ exome AF: 0.00

Gnomad EAS 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: 0.00000911 AC: 10 AN: 1098240 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 1 AN XY: 363594

African (AFR) AF: 0.00 AC: 0 AN: 26403

American (AMR) AF: 0.0000568 AC: 2 AN: 35207

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19386

East Asian (EAS) AF: 0.00 AC: 0 AN: 30206

South Asian (SAS) AF: 0.00 AC: 0 AN: 54147

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40534

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4137

European-Non Finnish (NFE) AF: 0.00000831 AC: 7 AN: 842122

Other (OTH) AF: 0.0000217 AC: 1 AN: 46098

GnomAD4 genome AF: 0.0000365 AC: 4 AN: 109661 Hom.: 0 Cov.: 20 AF XY: 0.0000314 AC XY: 1 AN XY: 31891

African (AFR) AF: 0.0000333 AC: 1 AN: 30043

American (AMR) AF: 0.000195 AC: 2 AN: 10261

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2635

East Asian (EAS) AF: 0.00 AC: 0 AN: 3501

South Asian (SAS) AF: 0.00 AC: 0 AN: 2500

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5672

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 236

European-Non Finnish (NFE) AF: 0.0000190 AC: 1 AN: 52682

Other (OTH) AF: 0.00 AC: 0 AN: 1449

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000642

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.0
DANN	Benign	0.95
DEOGEN2	Benign	0.035	T
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.24	T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		0.44
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.090
Sift	Benign	0.071	T
Sift4G	Benign	0.45	T
Polyphen		0.0010	B
Vest4		0.21
MutPred		0.66		Loss of helix (P = 0.1299)
MVP		0.40
MPC		0.29
ClinPred		0.088	T
GERP RS		0.96
Varity_R		0.091
gMVP		0.040
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs946251881; hg19: chrX-101409094;