Variant 18-5397140-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_012307.5(EPB41L3):c.2759C>A(p.Ala920Asp) variant causes a missense change. The variant allele was found at a frequency of 0.000168 in 1,614,048 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A920V) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

EPB41L3
NM_012307.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.02

Variant links:

Genes affected

EPB41L3 (HGNC:3380): (erythrocyte membrane protein band 4.1 like 3) Predicted to enable cytoskeletal protein-membrane anchor activity. Predicted to be a structural constituent of cytoskeleton. Predicted to be involved in several processes, including nervous system development; paranodal junction maintenance; and protein localization to paranode region of axon. Located in cell-cell junction and plasma membrane. Biomarker of meningioma. [provided by Alliance of Genome Resources, Apr 2022]

EPB41L3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.16323552).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPB41L3	NM_012307.5 linkuse as main transcript	c.2759C>A	p.Ala920Asp	missense_variant	18/23	ENST00000341928.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPB41L3	ENST00000341928.7 linkuse as main transcript	c.2759C>A	p.Ala920Asp	missense_variant	18/23	1	NM_012307.5		Q9Y2J2-1

Frequencies

GnomAD3 genomes

AF:

0.000158

AC:

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.000338

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000796

AC:

AN:

251360

Hom.:

AF XY:

0.0000515

AC XY:

AN XY:

135828

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:

0.000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000169

AC:

247

AN:

1461832

Hom.:

Cov.:

AF XY:

0.000166

AC XY:

121

AN XY:

727218

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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:

0.000215

Gnomad4 OTH exome

AF:

0.0000993

GnomAD4 genome

AF:

0.000158

AC:

AN:

152216

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.0000241

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:

0.000338

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000427

Hom.:

Bravo

AF:

0.000128

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000659

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.0000593

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

Mar 29, 2022

The c.2759C>A (p.A920D) alteration is located in exon 18 (coding exon 17) of the EPB41L3 gene. This alteration results from a C to A substitution at nucleotide position 2759, causing the alanine (A) at amino acid position 920 to be replaced by an aspartic acid (D). 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

0.15

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.36

Cadd

Benign

Dann

Benign

0.96

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.25

FATHMM_MKL

Benign

0.69

LIST_S2

Uncertain

0.93

D;D;D;D;D;D

M_CAP

Benign

0.046

MetaRNN

Benign

0.16

T;T;T;T;T;T

MetaSVM

Benign

-0.87

MutationTaster

Benign

1.0

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

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.78

N;.;N;.;.;.

REVEL

Benign

0.15

Sift

Uncertain

0.0040

D;.;D;.;.;.

Sift4G

Benign

0.20

T;T;T;.;T;T

Polyphen

0.46, 0.71, 0.0010

.;.;P;.;P;B

Vest4

0.52

MVP

0.73

MPC

0.40

ClinPred

0.16

GERP RS

4.0

Varity_R

0.18

gMVP

0.54

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

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