X-103063037-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_018476.4(BEX1):​c.238G>A​(p.Glu80Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000728 in 1,098,270 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 0.0000073 (0 hom. 1 hem.)
• Consequence: BEX1 NM_018476.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.46

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30724186).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BEX1	NM_018476.4	c.238G>A	p.Glu80Lys	missense_variant	Exon 3 of 3	ENST00000372728.4	NP_060946.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BEX1	ENST00000372728.4	c.238G>A	p.Glu80Lys	missense_variant	Exon 3 of 3	1	NM_018476.4	ENSP00000361813.3

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 0.00000728 AC: 8 AN: 1098270 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 1 AN XY: 363624

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000185

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000831

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 22

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 22, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.238G>A (p.E80K) alteration is located in exon 3 (coding exon 1) of the BEX1 gene. This alteration results from a G to A substitution at nucleotide position 238, causing the glutamic acid (E) at amino acid position 80 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.32	T
FATHMM_MKL	Benign	0.0073	N
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.084	D
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.12
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.016	D
Polyphen		0.98	D
Vest4		0.19
MutPred		0.60		Gain of MoRF binding (P = 6e-04);
MVP		0.21
MPC		0.38
ClinPred		0.97	D
GERP RS		3.3
Varity_R		0.31
gMVP		0.27

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

Publications

LitVar

Other links and lift over

dbSNP: rs985774587; hg19: chrX-102317965;