X-102154002-C-G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -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
• 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 -4 ACMG points.

• BS2: High Hemizygotes in GnomAdExome4 at 4 gene

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.264G>C	p.Arg88Ser	missense	Exon 3 of 3	NP_001012996.1	Q5H9J7
	BEX5	NM_001159560.2		c.264G>C	p.Arg88Ser	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.264G>C	p.Arg88Ser	missense	Exon 3 of 3	ENSP00000328030.3	Q5H9J7
	BEX5	ENST00000543160.5	TSL:3	c.264G>C	p.Arg88Ser	missense	Exon 3 of 3	ENSP00000446054.1	Q5H9J7
	BEX5	ENST00000883041.1		c.264G>C	p.Arg88Ser	missense	Exon 2 of 2	ENSP00000553100.1

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

African (AFR) AF: 0.00 AC: 0 AN: 26397

American (AMR) AF: 0.00 AC: 0 AN: 35205

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19383

East Asian (EAS) AF: 0.00 AC: 0 AN: 30205

South Asian (SAS) AF: 0.00 AC: 0 AN: 54131

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40533

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

European-Non Finnish (NFE) AF: 0.0000166 AC: 14 AN: 842004

Other (OTH) AF: 0.0000217 AC: 1 AN: 46082

GnomAD4 genome Cov.: 20

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.92
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.024	T
FATHMM_MKL	Benign	0.43	N
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.0045	T
MetaRNN	Uncertain	0.60	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L
PhyloP100		-0.37
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.25
Sift	Benign	0.36	T
Sift4G	Benign	1.0	T
Polyphen		1.0	D
Vest4		0.52
MutPred		0.55		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
Mutation Taster		=89/11	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: rs1416948596; hg19: chrX-101408974;