X-48523821-G-C

Variant names:

• chrX-48523821-G-C
• NM_006579.3:c.50G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006579.3(EBP):​c.50G>C​(p.Arg17Thr) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 21)
• Consequence: EBP NM_006579.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.283

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]

ENSG00000286268 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14616588).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EBP	NM_006579.3	c.50G>C	p.Arg17Thr	missense_variant	Exon 2 of 5	ENST00000495186.6	NP_006570.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EBP	ENST00000495186.6	c.50G>C	p.Arg17Thr	missense_variant	Exon 2 of 5	1	NM_006579.3	ENSP00000417052.1
ENSG00000286268	ENST00000651615.1	c.50G>C	p.Arg17Thr	missense_variant	Exon 2 of 7			ENSP00000498524.1

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 21

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Chondrodysplasia punctata 2 X-linked dominant;C4085243:MEND syndrome Uncertain:1

May 07, 2024

Fulgent Genetics, Fulgent Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.060
CADD	Benign	1.9
DANN	Benign	0.58
DEOGEN2	Benign	0.35	T;T;.
FATHMM_MKL	Benign	0.039	N
LIST_S2	Benign	0.64	T;T;T
M_CAP	Uncertain	0.26	D
MetaRNN	Benign	0.15	T;T;T
MetaSVM	Uncertain	0.22	D
MutationAssessor	Uncertain	2.6	M;.;.
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.55	N;N;N
REVEL	Uncertain	0.42
Sift	Benign	0.34	T;T;T
Sift4G	Benign	0.50	T;T;T
Polyphen		0.15	B;.;.
Vest4		0.17
MutPred		0.35		Loss of solvent accessibility (P = 0.0769);Loss of solvent accessibility (P = 0.0769);Loss of solvent accessibility (P = 0.0769);
MVP		0.92
MPC		0.92
ClinPred		0.15	T
GERP RS		-2.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.20
gMVP		0.77

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-48382209;