X-102154002-C-G

Variant names:

• chrX-102154002-C-G
• rs1416948596
• NM_001012978.3:c.264G>C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001012978.3(BEX5):​c.264G>C​(p.Arg88Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000137 in 1,098,077 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 20)
  • Exomes 𝑓: 0.000014 (0 hom. 4 hem.)
• Consequence: BEX5 NM_001012978.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.373

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 Likely_benign. Variant got -4 ACMG points.

• BS2: High Hemizygotes in GnomAdExome4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BEX5	NM_001012978.3	c.264G>C	p.Arg88Ser	missense_variant	Exon 3 of 3	ENST00000333643.4	NP_001012996.1
BEX5	NM_001159560.2	c.264G>C	p.Arg88Ser	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.264G>C	p.Arg88Ser	missense_variant	Exon 3 of 3	1	NM_001012978.3	ENSP00000328030.3
BEX5	ENST00000543160.5	c.264G>C	p.Arg88Ser	missense_variant	Exon 3 of 3	3		ENSP00000446054.1

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD4 exome AF: 0.0000137 AC: 15 AN: 1098077 Hom.: 0 Cov.: 30 AF XY: 0.0000110 AC XY: 4 AN XY: 363431

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000166

Gnomad4 OTH exome AF: 0.0000217

GnomAD4 genome Cov.: 20

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 14, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.264G>C (p.R88S) alteration is located in exon 3 (coding exon 1) of the BEX5 gene. This alteration results from a G to C substitution at nucleotide position 264, causing the arginine (R) at amino acid position 88 to be replaced by a serine (S). 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	0.92
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.024	T;T
FATHMM_MKL	Benign	0.43	N
LIST_S2	Benign	0.80	T;.
M_CAP	Benign	0.0045	T
MetaRNN	Uncertain	0.60	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L;L
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-1.5	N;N
REVEL	Benign	0.25
Sift	Benign	0.36	T;T
Sift4G	Benign	1.0	T;T
Polyphen		1.0	D;D
Vest4		0.52
MutPred		0.55		Loss of MoRF binding (P = 0.0326);Loss of MoRF binding (P = 0.0326);
MVP		0.90
MPC		0.91
ClinPred		0.85	D
GERP RS		2.2
Varity_R		0.22
gMVP		0.24

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

LitVar

Other links and lift over

dbSNP: rs1416948596; hg19: chrX-101408974;