NM_001012978.3:c.187G>A

Variant names:

• chrX-102154079-C-T
• NM_001012978.3:c.187G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.968
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38210577).

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.187G>A	p.Gly63Arg	missense	Exon 3 of 3	NP_001012996.1	Q5H9J7
	BEX5	NM_001159560.2		c.187G>A	p.Gly63Arg	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.187G>A	p.Gly63Arg	missense	Exon 3 of 3	ENSP00000328030.3	Q5H9J7
	BEX5	ENST00000543160.5	TSL:3	c.187G>A	p.Gly63Arg	missense	Exon 3 of 3	ENSP00000446054.1	Q5H9J7
	BEX5	ENST00000883041.1		c.187G>A	p.Gly63Arg	missense	Exon 2 of 2	ENSP00000553100.1

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 20

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	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
FATHMM_MKL	Benign	0.39	N
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.38	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		0.97
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	0.31	N
REVEL	Benign	0.17
Sift	Benign	0.29	T
Sift4G	Benign	0.59	T
Polyphen		1.0	D
Vest4		0.35
MutPred		0.40		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
Mutation Taster		=94/6	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

hg19: chrX-101409051;