X-103063247-T-C

Variant names:

• chrX-103063247-T-C
• NM_018476.4:c.28A>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.28A>G​(p.Asn10Asp) 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. 14/21 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: 2.49
• 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=0.13235009).

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.28A>G	p.Asn10Asp	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.28A>G	p.Asn10Asp	missense	Exon 3 of 3	ENSP00000361813.3	Q9HBH7
	BEX1	ENST00000885580.1		c.28A>G	p.Asn10Asp	missense	Exon 2 of 2	ENSP00000555639.1
	BEX1	ENST00000885581.1		c.28A>G	p.Asn10Asp	missense	Exon 2 of 2	ENSP00000555640.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 30

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	0.079
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.92
CADD	Benign	16
DANN	Benign	0.96
DEOGEN2	Uncertain	0.42	T
FATHMM_MKL	Benign	0.0064	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
PhyloP100		2.5
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.027
Sift	Benign	0.034	D
Sift4G	Uncertain	0.041	D
Polyphen		0.039	B
Vest4		0.12
MutPred		0.16		Loss of MoRF binding (P = 0.0399)
MVP		0.23
MPC		0.079
ClinPred		0.20	T
GERP RS		3.3
Varity_R		0.19
gMVP		0.11
Mutation Taster		=100/0	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-102318175;