X-102154099-T-C

Variant names:

• chrX-102154099-T-C
• rs1293969870
• NM_001012978.3:c.167A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001012978.3(BEX5):​c.167A>G​(p.Asp56Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000108 in 1,207,335 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000092 (0 hom., 0 hem., cov: 20)
  • Exomes 𝑓: 0.000011 (0 hom. 1 hem.)
• Consequence: BEX5 NM_001012978.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.22
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21483472).

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.167A>G	p.Asp56Gly	missense	Exon 3 of 3	NP_001012996.1	Q5H9J7
	BEX5	NM_001159560.2		c.167A>G	p.Asp56Gly	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.167A>G	p.Asp56Gly	missense	Exon 3 of 3	ENSP00000328030.3	Q5H9J7
	BEX5	ENST00000543160.5	TSL:3	c.167A>G	p.Asp56Gly	missense	Exon 3 of 3	ENSP00000446054.1	Q5H9J7
	BEX5	ENST00000883041.1		c.167A>G	p.Asp56Gly	missense	Exon 2 of 2	ENSP00000553100.1

Frequencies

GnomAD3 genomes AF: 0.00000917 AC: 1 AN: 109080 Hom.: 0 Cov.: 20

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000190

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000545 AC: 1 AN: 183506 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000365

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000109 AC: 12 AN: 1098255 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 1 AN XY: 363609

African (AFR) AF: 0.00 AC: 0 AN: 26403

American (AMR) AF: 0.0000284 AC: 1 AN: 35206

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19386

East Asian (EAS) AF: 0.00 AC: 0 AN: 30206

South Asian (SAS) AF: 0.00 AC: 0 AN: 54147

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40534

Middle Eastern (MID) AF: 0.000242 AC: 1 AN: 4137

European-Non Finnish (NFE) AF: 0.0000107 AC: 9 AN: 842138

Other (OTH) AF: 0.0000217 AC: 1 AN: 46098

GnomAD4 genome AF: 0.00000917 AC: 1 AN: 109080 Hom.: 0 Cov.: 20 AF XY: 0.00 AC XY: 0 AN XY: 31344

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 29867

American (AMR) AF: 0.00 AC: 0 AN: 10198

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2622

East Asian (EAS) AF: 0.00 AC: 0 AN: 3482

South Asian (SAS) AF: 0.00 AC: 0 AN: 2463

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5568

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 237

European-Non Finnish (NFE) AF: 0.0000190 AC: 1 AN: 52512

Other (OTH) AF: 0.00 AC: 0 AN: 1450

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

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	Benign	0.13
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.024	T
FATHMM_MKL	Benign	0.45	N
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L
PhyloP100		2.2
PrimateAI	Uncertain	0.68	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.15
Sift	Benign	0.049	D
Sift4G	Benign	0.44	T
Polyphen		0.19	B
Vest4		0.16
MutPred		0.55		Loss of stability (P = 0.028)
MVP		0.51
MPC		0.37
ClinPred		0.19	T
GERP RS		4.0
Varity_R		0.32
gMVP		0.070
Mutation Taster		=95/5	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: rs1293969870; hg19: chrX-101409071;