rs985774587

Variant names:

• chrX-103063037-C-G
• rs985774587
• NM_018476.4:c.238G>C

Your query was ambiguous. Multiple possible variants found:

• chrX-103063037-C-G
• chrX-103063037-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_018476.4(BEX1):​c.238G>C​(p.Glu80Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000009 in 111,110 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E80K) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000090 (0 hom., 0 hem., cov: 22)
• Consequence: BEX1 NM_018476.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.46
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.303679).

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.238G>C	p.Glu80Gln	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.238G>C	p.Glu80Gln	missense	Exon 3 of 3	ENSP00000361813.3	Q9HBH7
	BEX1	ENST00000885580.1		c.238G>C	p.Glu80Gln	missense	Exon 2 of 2	ENSP00000555639.1
	BEX1	ENST00000885581.1		c.238G>C	p.Glu80Gln	missense	Exon 2 of 2	ENSP00000555640.1

Frequencies

GnomAD3 genomes AF: 0.00000900 AC: 1 AN: 111110 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.0000328

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000900 AC: 1 AN: 111110 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 33268

African (AFR) AF: 0.0000328 AC: 1 AN: 30505

American (AMR) AF: 0.00 AC: 0 AN: 10432

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2640

East Asian (EAS) AF: 0.00 AC: 0 AN: 3517

South Asian (SAS) AF: 0.00 AC: 0 AN: 2598

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5962

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53042

Other (OTH) AF: 0.00 AC: 0 AN: 1497

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.33	T
FATHMM_MKL	Benign	0.0091	N
LIST_S2	Benign	0.72	T
M_CAP	Uncertain	0.086	D
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		2.5
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.11
Sift	Uncertain	0.018	D
Sift4G	Uncertain	0.020	D
Polyphen		1.0	D
Vest4		0.15
MutPred		0.58		Gain of MoRF binding (P = 0.0147)
MVP		0.12
MPC		0.39
ClinPred		0.90	D
GERP RS		3.3
Varity_R		0.26
gMVP		0.16
Mutation Taster		=99/1	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: rs985774587; hg19: chrX-102317965;