rs149737043
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_006393.3(NEBL):c.904C>T(p.Arg302Ter) variant causes a stop gained, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00002 in 1,599,632 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_006393.3 stop_gained, splice_region
Scores
Clinical Significance
Conservation
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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.904C>T | p.Arg302Ter | stop_gained, splice_region_variant | 10/28 | ENST00000377122.9 | |
LOC102725112 | XR_007062082.1 | n.223+4123G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NEBL | ENST00000377122.9 | c.904C>T | p.Arg302Ter | stop_gained, splice_region_variant | 10/28 | 1 | NM_006393.3 |
Frequencies
GnomAD3 genomes AF: 0.0000395 AC: 6AN: 152034Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000481 AC: 12AN: 249242Hom.: 0 AF XY: 0.0000297 AC XY: 4AN XY: 134710
GnomAD4 exome AF: 0.0000180 AC: 26AN: 1447598Hom.: 0 Cov.: 29 AF XY: 0.0000166 AC XY: 12AN XY: 720956
GnomAD4 genome AF: 0.0000395 AC: 6AN: 152034Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5AN XY: 74270
ClinVar
Submissions by phenotype
Primary dilated cardiomyopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 19, 2022 | 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 580927). This variant has not been reported in the literature in individuals affected with NEBL-related conditions. This variant is present in population databases (rs149737043, gnomAD 0.02%). This sequence change creates a premature translational stop signal (p.Arg302*) in the NEBL gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in NEBL cause disease. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at