rs587783620

chrX-48528445-CAAG-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM1 PM4_Supporting

The NM_006579.3(EBP):c.687_689del(p.Lys229del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.0000133 in 1,053,616 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 0.000013 (0 hom. 2 hem.)
• Consequence: EBP NM_006579.3 inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 5.68

Genes affected

EBP (HGNC:3133): (EBP cholestenol delta-isomerase) The protein encoded by this gene is an integral membrane protein of the endoplasmic reticulum. It is a high affinity binding protein for the antiischemic phenylalkylamine Ca2+ antagonist [3H]emopamil and the photoaffinity label [3H]azidopamil. It is similar to sigma receptors and may be a member of a superfamily of high affinity drug-binding proteins in the endoplasmic reticulum of different tissues. This protein shares structural features with bacterial and eukaryontic drug transporting proteins. It has four putative transmembrane segments and contains two conserved glutamate residues which may be involved in the transport of cationic amphiphilics. Another prominent feature of this protein is its high content of aromatic amino acid residues (>23%) in its transmembrane segments. These aromatic amino acid residues have been suggested to be involved in the drug transport by the P-glycoprotein. Mutations in this gene cause Chondrodysplasia punctata 2 (CDPX2; also known as Conradi-Hunermann syndrome). [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM1: In a chain 3-beta-hydroxysteroid-Delta(8),Delta(7)-isomerase (size 228) in uniprot entity EBP_HUMAN there are 35 pathogenic changes around while only 14 benign (71%) in NM_006579.3
• PM4: Nonframeshift variant in NON repetitive region in NM_006579.3. Strenght limited to Supporting due to length of the change: 1aa.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EBP	NM_006579.3	c.687_689del	p.Lys229del	inframe_deletion	5/5	ENST00000495186.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EBP	ENST00000495186.6	c.687_689del	p.Lys229del	inframe_deletion	5/5	1	NM_006579.3	P1
EBP	ENST00000276096.10	n.645_647del		non_coding_transcript_exon_variant	5/5	2
EBP	ENST00000498425.1			downstream_gene_variant		3

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 0.0000133 AC: 14 AN: 1053616 Hom.: 0 AF XY: 0.00000582 AC XY: 2 AN XY: 343770

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000159

Gnomad4 OTH exome AF: 0.0000225

GnomAD4 genome Cov.: 22

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Invitae

Sep 01, 2022

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 158554). This variant has not been reported in the literature in individuals affected with EBP-related conditions. This variant is not present in population databases (gnomAD no frequency). This variant, c.687_689del, results in the deletion of 1 amino acid(s) of the EBP protein (p.Lys229del), but otherwise preserves the integrity of the reading frame. -

Chondrodysplasia punctata 2 X-linked dominant Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Feb 08, 2013

- -

Computational scores

Source: dbNSFP v4.3

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: rs587783620; hg19: chrX-48386833;