chr13-49661177-C-G

Position:

• chr13-49661177-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_032565.5(EBPL):​c.412G>C​(p.Glu138Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: EBPL NM_032565.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.49

Genes affected

EBPL (HGNC:18061): (EBP like) Predicted to enable cholestenol delta-isomerase activity. Predicted to be involved in sterol metabolic process. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.821

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EBPL	NM_032565.5	c.412G>C	p.Glu138Gln	missense_variant	4/4	ENST00000242827.11	NP_115954.1
EBPL	NM_001278636.1	c.*69G>C		3_prime_UTR_variant	5/5		NP_001265565.1
EBPL	NR_103802.1	n.596G>C		non_coding_transcript_exon_variant	5/5
EBPL	NR_103803.1	n.405G>C		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EBPL	ENST00000242827.11	c.412G>C	p.Glu138Gln	missense_variant	4/4	1	NM_032565.5	ENSP00000242827	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 29, 2023

The c.412G>C (p.E138Q) alteration is located in exon 4 (coding exon 4) of the EBPL gene. This alteration results from a G to C substitution at nucleotide position 412, causing the glutamic acid (E) at amino acid position 138 to be replaced by a glutamine (Q). 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	0.24
BayesDel_addAF	Pathogenic	0.43	D
BayesDel_noAF	Pathogenic	0.37
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.68	D
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.046	D
MetaRNN	Pathogenic	0.82	D
MetaSVM	Benign	-0.52	T
MutationAssessor	Benign	1.9	M
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.65	T
PROVEAN	Uncertain	-2.9	D
REVEL	Pathogenic	0.71
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.70
MutPred		0.53		Gain of catalytic residue at W143 (P = 0);
MVP		0.91
MPC		1.1
ClinPred		0.98	D
GERP RS		5.6
Varity_R		0.72
gMVP		0.73

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: rs754650479; hg19: chr13-50235313;