2-151576269-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001164507.2(NEB):āc.16790C>Gā(p.Ala5597Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,610,926 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A5597T) 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.16790C>G | p.Ala5597Gly | missense_variant | 106/182 | ENST00000427231.7 | |
NEB | NM_001164508.2 | c.16790C>G | p.Ala5597Gly | missense_variant | 106/182 | ENST00000397345.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NEB | ENST00000397345.8 | c.16790C>G | p.Ala5597Gly | missense_variant | 106/182 | 5 | NM_001164508.2 | P5 | |
NEB | ENST00000427231.7 | c.16790C>G | p.Ala5597Gly | missense_variant | 106/182 | 5 | NM_001164507.2 | A2 | |
NEB | ENST00000409198.5 | c.11687C>G | p.Ala3896Gly | missense_variant | 79/150 | 5 | |||
NEB | ENST00000413693.5 | c.980C>G | p.Ala327Gly | missense_variant | 6/74 | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000397 AC: 6AN: 151300Hom.: 0 Cov.: 30
GnomAD3 exomes AF: 0.0000201 AC: 5AN: 249058Hom.: 0 AF XY: 0.00000740 AC XY: 1AN XY: 135110
GnomAD4 exome AF: 0.00000822 AC: 12AN: 1459626Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3AN XY: 726140
GnomAD4 genome AF: 0.0000397 AC: 6AN: 151300Hom.: 0 Cov.: 30 AF XY: 0.0000135 AC XY: 1AN XY: 73900
ClinVar
Submissions by phenotype
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 alanine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 5597 of the NEB protein (p.Ala5597Gly). This variant is present in population databases (rs777969701, gnomAD 0.004%). 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: 465496). 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 | Aug 08, 2019 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at