NM_018476.4:c.46A>G

Variant names:

• chrX-103063229-T-C
• NM_018476.4:c.46A>G

Variant summary

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

The NM_018476.4(BEX1):​c.46A>G​(p.Asn16Asp) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 22)
• Consequence: BEX1 NM_018476.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.00700
• Publications: 0 publications found

Genes affected

BEX1 (HGNC:1036): (brain expressed X-linked 1) Enables RNA polymerase II-specific DNA-binding transcription factor binding activity. Involved in positive regulation of DNA-binding transcription factor activity and positive regulation of transcription by RNA polymerase II. Part of transcription regulator complex. [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=0.11616856).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018476.4. 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
	BEX1	NM_018476.4	MANE Select	c.46A>G	p.Asn16Asp	missense	Exon 3 of 3	NP_060946.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BEX1	ENST00000372728.4	TSL:1 MANE Select	c.46A>G	p.Asn16Asp	missense	Exon 3 of 3	ENSP00000361813.3	Q9HBH7
	BEX1	ENST00000885580.1		c.46A>G	p.Asn16Asp	missense	Exon 2 of 2	ENSP00000555639.1
	BEX1	ENST00000885581.1		c.46A>G	p.Asn16Asp	missense	Exon 2 of 2	ENSP00000555640.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 22

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	0.099
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	13
DANN	Benign	0.97
DEOGEN2	Benign	0.31	T
FATHMM_MKL	Benign	0.00097	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PhyloP100		-0.0070
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-3.8	D
REVEL	Benign	0.037
Sift	Benign	0.088	T
Sift4G	Benign	0.067	T
Polyphen		0.0010	B
Vest4		0.13
MutPred		0.40		Loss of MoRF binding (P = 0.0661)
MVP		0.28
MPC		0.084
ClinPred		0.066	T
GERP RS		3.3
Varity_R		0.33
gMVP		0.21
Mutation Taster		=98/2	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

hg19: chrX-102318157;