chr3-25764272-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_018297.4(NGLY1):c.286G>A(p.Glu96Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000929 in 1,613,794 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 (★). Synonymous variant affecting the same amino acid position (i.e. E96E) has been classified as Likely benign.
Frequency
Consequence
NM_018297.4 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 |
---|---|---|---|---|---|---|---|
NGLY1 | NM_018297.4 | c.286G>A | p.Glu96Lys | missense_variant | 3/12 | ENST00000280700.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NGLY1 | ENST00000280700.10 | c.286G>A | p.Glu96Lys | missense_variant | 3/12 | 1 | NM_018297.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 151998Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000160 AC: 4AN: 250774Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135506
GnomAD4 exome AF: 0.00000684 AC: 10AN: 1461796Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5AN XY: 727200
GnomAD4 genome AF: 0.0000329 AC: 5AN: 151998Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74222
ClinVar
Submissions by phenotype
Congenital disorder of deglycosylation Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 14, 2022 | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 96 of the NGLY1 protein (p.Glu96Lys). This variant is present in population databases (rs777476251, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with NGLY1-related conditions. ClinVar contains an entry for this variant (Variation ID: 541258). 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: "Benign"; 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