rs757784515
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4BP6
The NM_001164507.2(NEB):āc.3373G>Cā(p.Glu1125Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,613,756 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 Conflicting classifications of pathogenicity (no stars).
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.3373G>C | p.Glu1125Gln | missense_variant | 33/182 | ENST00000427231.7 | |
NEB | NM_001164508.2 | c.3373G>C | p.Glu1125Gln | missense_variant | 33/182 | ENST00000397345.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NEB | ENST00000397345.8 | c.3373G>C | p.Glu1125Gln | missense_variant | 33/182 | 5 | NM_001164508.2 | P5 | |
NEB | ENST00000427231.7 | c.3373G>C | p.Glu1125Gln | missense_variant | 33/182 | 5 | NM_001164507.2 | A2 | |
NEB | ENST00000409198.5 | c.3373G>C | p.Glu1125Gln | missense_variant | 33/150 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152120Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000401 AC: 1AN: 249076Hom.: 0 AF XY: 0.00000740 AC XY: 1AN XY: 135110
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461636Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727108
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152120Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74300
ClinVar
Submissions by phenotype
Nemaline myopathy 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 13, 2022 | This sequence change replaces glutamic acid, which is acidic and polar, with glutamine, which is neutral and polar, at codon 1125 of the NEB protein (p.Glu1125Gln). This variant is present in population databases (rs757784515, gnomAD 0.0009%). 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: 257809). 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 specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at