rs765379397
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001164507.2(NEB):c.11234G>T(p.Arg3745Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000341 in 1,612,978 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 Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R3745H) 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 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NEB | NM_001164507.2 | c.11234G>T | p.Arg3745Leu | missense_variant | 76/182 | ENST00000427231.7 | |
NEB | NM_001164508.2 | c.11234G>T | p.Arg3745Leu | missense_variant | 76/182 | ENST00000397345.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NEB | ENST00000397345.8 | c.11234G>T | p.Arg3745Leu | missense_variant | 76/182 | 5 | NM_001164508.2 | P5 | |
NEB | ENST00000427231.7 | c.11234G>T | p.Arg3745Leu | missense_variant | 76/182 | 5 | NM_001164507.2 | A2 | |
NEB | ENST00000409198.5 | c.10505G>T | p.Arg3502Leu | missense_variant | 73/150 | 5 | |||
NEB | ENST00000486320.1 | n.175G>T | non_coding_transcript_exon_variant | 2/2 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152024Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000169 AC: 42AN: 247892Hom.: 0 AF XY: 0.000112 AC XY: 15AN XY: 134472
GnomAD4 exome AF: 0.0000356 AC: 52AN: 1460954Hom.: 0 Cov.: 30 AF XY: 0.0000275 AC XY: 20AN XY: 726726
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152024Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74242
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Oct 04, 2023 | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Aug 23, 2023 | - - |
Nemaline myopathy 2 Uncertain:2
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Nov 11, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 04, 2022 | This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 3745 of the NEB protein (p.Arg3745Leu). This variant is present in population databases (rs765379397, gnomAD 0.1%). 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: 465435). 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at