rs750748717
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001164507.2(NEB):c.11581G>T(p.Ala3861Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000013 in 1,613,666 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. A3861T) 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 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NEB | NM_001164507.2 | c.11581G>T | p.Ala3861Ser | missense_variant | 77/182 | ENST00000427231.7 | |
NEB | NM_001164508.2 | c.11581G>T | p.Ala3861Ser | missense_variant | 77/182 | ENST00000397345.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NEB | ENST00000397345.8 | c.11581G>T | p.Ala3861Ser | missense_variant | 77/182 | 5 | NM_001164508.2 | P5 | |
NEB | ENST00000427231.7 | c.11581G>T | p.Ala3861Ser | missense_variant | 77/182 | 5 | NM_001164507.2 | A2 | |
NEB | ENST00000409198.5 | c.10852G>T | p.Ala3618Ser | missense_variant | 74/150 | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152178Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000402 AC: 1AN: 248504Hom.: 0 AF XY: 0.00000742 AC XY: 1AN XY: 134806
GnomAD4 exome AF: 0.0000116 AC: 17AN: 1461488Hom.: 0 Cov.: 31 AF XY: 0.0000151 AC XY: 11AN XY: 727006
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152178Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74336
ClinVar
Submissions by phenotype
Nemaline myopathy 2 Uncertain:2
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 10, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 06, 2022 | This sequence change replaces alanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 3861 of the NEB protein (p.Ala3861Ser). This variant is present in population databases (rs750748717, gnomAD 0.003%). This missense change has been observed in individual(s) with NEB-related conditions (Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 449660). 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 | GeneDx | Dec 16, 2019 | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Reported as a variant of uncertain significance in ClinVar but additional evidence is not available (ClinVar SCV000829230.1; Landrum et al., 2016); Has not been previously published as pathogenic or benign to our knowledge - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at