rs777069327
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_018297.4(NGLY1):c.1808A>T(p.Tyr603Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,400 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/16 in silico tools predict 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. Y603C) has been classified as Uncertain significance.
Frequency
Consequence
NM_018297.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NGLY1 | NM_018297.4 | c.1808A>T | p.Tyr603Phe | missense_variant | 12/12 | ENST00000280700.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NGLY1 | ENST00000280700.10 | c.1808A>T | p.Tyr603Phe | missense_variant | 12/12 | 1 | NM_018297.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461400Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727018
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Congenital disorder of deglycosylation Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 15, 2021 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with NGLY1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces tyrosine with phenylalanine at codon 603 of the NGLY1 protein (p.Tyr603Phe). The tyrosine residue is moderately conserved and there is a small physicochemical difference between tyrosine and phenylalanine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.