X-102154079-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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

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

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
BEX5	NM_001012978.3	c.187G>A	p.Gly63Arg	missense_variant	Exon 3 of 3	ENST00000333643.4	NP_001012996.1
BEX5	NM_001159560.2	c.187G>A	p.Gly63Arg	missense_variant	Exon 3 of 3		NP_001153032.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BEX5	ENST00000333643.4	c.187G>A	p.Gly63Arg	missense_variant	Exon 3 of 3	1	NM_001012978.3	ENSP00000328030.3
BEX5	ENST00000543160.5	c.187G>A	p.Gly63Arg	missense_variant	Exon 3 of 3	3		ENSP00000446054.1

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

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;