rs189440246
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The ENST00000377122.9(NEBL):c.367G>A(p.Glu123Lys) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000708 in 1,596,450 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
ENST00000377122.9 missense, splice_region
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NEBL | NM_006393.3 | c.367G>A | p.Glu123Lys | missense_variant, splice_region_variant | 4/28 | ENST00000377122.9 | NP_006384.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NEBL | ENST00000377122.9 | c.367G>A | p.Glu123Lys | missense_variant, splice_region_variant | 4/28 | 1 | NM_006393.3 | ENSP00000366326 |
Frequencies
GnomAD3 genomes AF: 0.0000789 AC: 12AN: 152180Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000263 AC: 66AN: 251338Hom.: 0 AF XY: 0.000258 AC XY: 35AN XY: 135842
GnomAD4 exome AF: 0.0000699 AC: 101AN: 1444152Hom.: 0 Cov.: 30 AF XY: 0.0000820 AC XY: 59AN XY: 719772
GnomAD4 genome AF: 0.0000788 AC: 12AN: 152298Hom.: 0 Cov.: 33 AF XY: 0.000107 AC XY: 8AN XY: 74456
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 19, 2022 | The p.E123K variant (also known as c.367G>A), located in coding exon 4 of the NEBL gene, results from a G to A substitution at nucleotide position 367. The glutamic acid at codon 123 is replaced by lysine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
NEBL-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 10, 2024 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Primary dilated cardiomyopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Sep 15, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at