X-102154102-A-C

Variant names:

• chrX-102154102-A-C
• NM_001012978.3:c.164T>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001012978.3(BEX5):​c.164T>G​(p.Val55Gly) 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. 13/20 in silico tools predict 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: -0.275

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1837767).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BEX5	NM_001012978.3	c.164T>G	p.Val55Gly	missense_variant	Exon 3 of 3	ENST00000333643.4	NP_001012996.1
BEX5	NM_001159560.2	c.164T>G	p.Val55Gly	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.164T>G	p.Val55Gly	missense_variant	Exon 3 of 3	1	NM_001012978.3	ENSP00000328030.3
BEX5	ENST00000543160.5	c.164T>G	p.Val55Gly	missense_variant	Exon 3 of 3	3		ENSP00000446054.1

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 20

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 12, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.164T>G (p.V55G) alteration is located in exon 3 (coding exon 1) of the BEX5 gene. This alteration results from a T to G substitution at nucleotide position 164, causing the valine (V) at amino acid position 55 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	0.14
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	7.6
DANN	Benign	0.82
DEOGEN2	Benign	0.0049	T;T
FATHMM_MKL	Benign	0.068	N
LIST_S2	Benign	0.23	T;.
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.18	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.88	L;L
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-0.25	N;N
REVEL	Benign	0.11
Sift	Benign	0.17	T;T
Sift4G	Benign	0.48	T;T
Polyphen		0.30	B;B
Vest4		0.28
MutPred		0.69		Loss of stability (P = 0.0126);Loss of stability (P = 0.0126);
MVP		0.33
MPC		0.44
ClinPred		0.084	T
GERP RS		0.38
Varity_R		0.080
gMVP		0.11

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-101409074;