X-48523798-C-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PP3_ModerateBP6BS1BS2

The NM_006579.3(EBP):c.27C>G(p.His9Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000382 in 1,203,808 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 15 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H9D) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000056 ( 0 hom., 2 hem., cov: 21)

Exomes 𝑓: 0.000036 ( 0 hom. 13 hem. )

Consequence

EBP
NM_006579.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 0.202

Variant links:

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]

EBP links:

ENSG00000286268 (HGNC:):

ENSG00000286268 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.888

BP6

Variant X-48523798-C-G is Benign according to our data. Variant chrX-48523798-C-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 3598326.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0000559 (6/107418) while in subpopulation NFE AF= 0.0000962 (5/51998). AF 95% confidence interval is 0.0000376. There are 0 homozygotes in gnomad4. There are 2 alleles in male gnomad4 subpopulation. Median coverage is 21. This position pass quality control queck.

BS2

High Hemizygotes in GnomAd4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EBP	NM_006579.3 link	c.27C>G	p.His9Gln	missense_variant	Exon 2 of 5	ENST00000495186.6	NP_006570.1	Q15125A0A024QYX0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EBP	ENST00000495186.6 link	c.27C>G	p.His9Gln	missense_variant	Exon 2 of 5	1	NM_006579.3	ENSP00000417052.1		Q15125
ENSG00000286268	ENST00000651615.1 link	c.27C>G	p.His9Gln	missense_variant	Exon 2 of 7			ENSP00000498524.1		A0A494C0F3

Frequencies

GnomAD3 genomes

AF:

0.0000559

AC:

AN:

107418

Hom.:

Cov.:

AF XY:

0.0000668

AC XY:

AN XY:

29932

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000962

Gnomad OTH

AF:

0.000706

GnomAD3 exomes

AF:

0.0000506

AC:

AN:

177700

Hom.:

AF XY:

0.0000319

AC XY:

AN XY:

62620

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000102

Gnomad OTH exome

AF:

0.000227

GnomAD4 exome

AF:

0.0000365

AC:

AN:

1096390

Hom.:

Cov.:

AF XY:

0.0000359

AC XY:

AN XY:

361844

show subpopulations

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:

0.0000440

Gnomad4 OTH exome

AF:

0.0000652

GnomAD4 genome

AF:

0.0000559

AC:

AN:

107418

Hom.:

Cov.:

AF XY:

0.0000668

AC XY:

AN XY:

29932

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000962

Gnomad4 OTH

AF:

0.000706

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.0000680

ExAC

AF:

0.0000494

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Chondrodysplasia punctata 2 X-linked dominant;C4085243:MEND syndrome

Uncertain:1

Apr 19, 2024

Fulgent Genetics, Fulgent Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.87

BayesDel_addAF

Pathogenic

0.50

BayesDel_noAF

Pathogenic

0.67

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Pathogenic

0.88

D;D;.

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.70

T;T;T

M_CAP

Pathogenic

0.79

MetaRNN

Pathogenic

0.89

D;D;D

MetaSVM

Pathogenic

1.1

MutationAssessor

Pathogenic

3.4

M;.;.

PrimateAI

Uncertain

0.54

PROVEAN

Pathogenic

-7.2

D;D;D

REVEL

Pathogenic

0.84

Sift

Pathogenic

0.0

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

D;.;.

Vest4

0.97

MutPred

0.75

Gain of glycosylation at P7 (P = 0.1548);Gain of glycosylation at P7 (P = 0.1548);Gain of glycosylation at P7 (P = 0.1548);

MVP

1.0

MPC

1.6

ClinPred

0.58

GERP RS

0.086

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.97

gMVP

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over