rs369283016
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001164507.2(NEB):c.8647G>A(p.Val2883Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000446 in 1,613,818 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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. V2883A) has been classified as Uncertain significance.
Frequency
Consequence
NM_001164507.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NEB | NM_001164507.2 | c.8647G>A | p.Val2883Ile | missense_variant | 61/182 | ENST00000427231.7 | |
NEB | NM_001164508.2 | c.8647G>A | p.Val2883Ile | missense_variant | 61/182 | ENST00000397345.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NEB | ENST00000397345.8 | c.8647G>A | p.Val2883Ile | missense_variant | 61/182 | 5 | NM_001164508.2 | P5 | |
NEB | ENST00000427231.7 | c.8647G>A | p.Val2883Ile | missense_variant | 61/182 | 5 | NM_001164507.2 | A2 | |
NEB | ENST00000409198.5 | c.8647G>A | p.Val2883Ile | missense_variant | 61/150 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.000105 AC: 16AN: 152138Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000843 AC: 21AN: 249072Hom.: 0 AF XY: 0.000126 AC XY: 17AN XY: 135128
GnomAD4 exome AF: 0.0000383 AC: 56AN: 1461680Hom.: 0 Cov.: 32 AF XY: 0.0000564 AC XY: 41AN XY: 727122
GnomAD4 genome ? AF: 0.000105 AC: 16AN: 152138Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11AN XY: 74312
ClinVar
Submissions by phenotype
Nemaline myopathy 2 Uncertain:2
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Mar 11, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 06, 2022 | This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 2883 of the NEB protein (p.Val2883Ile). This variant is present in population databases (rs369283016, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with NEB-related conditions. ClinVar contains an entry for this variant (Variation ID: 533972). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). 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. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Nov 17, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at