18-5398090-T-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_012307.5(EPB41L3):c.2403A>T(p.Leu801Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000867 in 1,614,158 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000089 ( 0 hom. )
Consequence
EPB41L3
NM_012307.5 missense
NM_012307.5 missense
Scores
1
6
10
Clinical Significance
Conservation
PhyloP100: 0.0500
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]
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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=0.10796413).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EPB41L3 | NM_012307.5 | c.2403A>T | p.Leu801Phe | missense_variant | 17/23 | ENST00000341928.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EPB41L3 | ENST00000341928.7 | c.2403A>T | p.Leu801Phe | missense_variant | 17/23 | 1 | NM_012307.5 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152192Hom.: 0 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000239 AC: 6AN: 250942Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135756
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GnomAD4 exome AF: 0.00000889 AC: 13AN: 1461848Hom.: 0 Cov.: 31 AF XY: 0.0000151 AC XY: 11AN XY: 727232
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GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152310Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74468
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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 24, 2023 | The c.2403A>T (p.L801F) alteration is located in exon 17 (coding exon 16) of the EPB41L3 gene. This alteration results from a A to T substitution at nucleotide position 2403, causing the leucine (L) at amino acid position 801 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Pathogenic
Cadd
Benign
Dann
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
D;D;D;D;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T;T
MetaSVM
Uncertain
D
MutationTaster
Benign
D;D;D;D;D;D;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;.;.;.
REVEL
Uncertain
Sift
Benign
T;T;D;.;.;.
Sift4G
Benign
T;T;T;.;.;.
Polyphen
0.91
.;.;P;.;.;.
Vest4
MutPred
0.25
.;.;Loss of stability (P = 0.1418);.;.;.;
MVP
MPC
0.18
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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Score
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at