Variant 13-49691346-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_032565.5(EBPL):c.79G>A(p.Ala27Thr) 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: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

EBPL
NM_032565.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.26

Variant links:

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]

EBPL links:

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ACMG classification

Classification made for transcript

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=0.3196762).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
EBPL	NM_032565.5 linkuse as main transcript	c.79G>A	p.Ala27Thr	missense_variant	1/4	ENST00000242827.11	NP_115954.1
EBPL	NM_001278636.1 linkuse as main transcript	c.79G>A	p.Ala27Thr	missense_variant	1/5		NP_001265565.1
EBPL	NR_103802.1 linkuse as main transcript	n.142G>A		non_coding_transcript_exon_variant	1/5
EBPL	NR_103803.1 linkuse as main transcript	n.142G>A		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EBPL	ENST00000242827.11 linkuse as main transcript	c.79G>A	p.Ala27Thr	missense_variant	1/4	1	NM_032565.5	ENSP00000242827	P1	Q9BY08-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1204006

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

587180

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 31, 2023

The c.79G>A (p.A27T) alteration is located in exon 1 (coding exon 1) of the EBPL gene. This alteration results from a G to A substitution at nucleotide position 79, causing the alanine (A) at amino acid position 27 to be replaced by a threonine (T). 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

0.11

BayesDel_addAF

Uncertain

0.073

BayesDel_noAF

Benign

-0.13

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Uncertain

0.50

.;.;D;.;.

Eigen

Benign

-0.98

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.50

LIST_S2

Benign

0.71

T;T;T;T;T

M_CAP

Pathogenic

0.97

MetaRNN

Benign

0.32

T;T;T;T;T

MetaSVM

Uncertain

0.095

MutationAssessor

Benign

1.5

.;L;L;L;L

MutationTaster

Benign

1.0

N;N;N;N;N;N;N

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-0.77

N;N;N;D;N

REVEL

Uncertain

0.32

Sift

Benign

0.55

T;T;T;T;T

Sift4G

Benign

0.48

T;T;T;T;T

Polyphen

0.031, 0.025

.;.;B;.;B

Vest4

0.26

MutPred

0.50

Gain of catalytic residue at G25 (P = 0.0029);Gain of catalytic residue at G25 (P = 0.0029);Gain of catalytic residue at G25 (P = 0.0029);Gain of catalytic residue at G25 (P = 0.0029);Gain of catalytic residue at G25 (P = 0.0029);

MVP

0.65

MPC

0.68

ClinPred

0.20

GERP RS

-0.26

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.059

gMVP

0.11

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over