rs145770601
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_006393.3(NEBL):c.14T>C(p.Val5Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000338 in 1,599,238 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_006393.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NEBL | NM_006393.3 | c.14T>C | p.Val5Ala | missense_variant | 1/28 | ENST00000377122.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NEBL | ENST00000377122.9 | c.14T>C | p.Val5Ala | missense_variant | 1/28 | 1 | NM_006393.3 |
Frequencies
GnomAD3 genomes ? AF: 0.000164 AC: 25AN: 152182Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000351 AC: 8AN: 227930Hom.: 0 AF XY: 0.0000244 AC XY: 3AN XY: 122996
GnomAD4 exome AF: 0.0000200 AC: 29AN: 1447056Hom.: 0 Cov.: 31 AF XY: 0.0000167 AC XY: 12AN XY: 719296
GnomAD4 genome ? AF: 0.000164 AC: 25AN: 152182Hom.: 0 Cov.: 33 AF XY: 0.0000807 AC XY: 6AN XY: 74338
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Aug 22, 2012 | The Val5Ala variant in NEBL has been identified in 1/4406 African American chrom osomes from a broad population by the NHLBI Exome Sequencing Project (http://evs .gs.washington.edu/EVS; dbSNP rs145770601), though this could represent a presym ptomatic individual. Computational analyses (biochemical amino acid properties, conservation, AlignGVGD, and PolyPhen2) suggest that the variant may not impact the protein, though this information is not predictive enough to rule out pathog enicity. Additional information is needed to fully assess the variant's clinical significance. - |
Primary dilated cardiomyopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 21, 2024 | This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 5 of the NEBL protein (p.Val5Ala). This variant is present in population databases (rs145770601, gnomAD 0.07%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with dilated cardiomyopathy (PMID: 32746448). ClinVar contains an entry for this variant (Variation ID: 45481). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at