rs587777266
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PM4_SupportingPP5
The NM_018297.4(NGLY1):c.1205_1207delGAA(p.Arg402del) variant causes a disruptive inframe deletion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,526 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 30)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
NGLY1
NM_018297.4 disruptive_inframe_deletion
NM_018297.4 disruptive_inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.61
Publications
7 publications found
Genes affected
NGLY1 (HGNC:17646): (N-glycanase 1) This gene encodes an enzyme that catalyzes hydrolysis of an N(4)-(acetyl-beta-D-glucosaminyl) asparagine residue to N-acetyl-beta-D-glucosaminylamine and a peptide containing an aspartate residue. The encoded enzyme may play a role in the proteasome-mediated degradation of misfolded glycoproteins. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Feb 2009]
NGLY1 Gene-Disease associations (from GenCC):
- congenital disorder of deglycosylation 1Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), G2P
- NGLY1-deficiencyInheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, PanelApp Australia
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in NM_018297.4. Strenght limited to Supporting due to length of the change: 1aa.
PP5
Variant 3-25733924-GTTC-G is Pathogenic according to our data. Variant chr3-25733924-GTTC-G is described in ClinVar as Pathogenic. ClinVar VariationId is 126423.Status of the report is no_assertion_criteria_provided, 0 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_018297.4. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| NGLY1 | NM_018297.4 | MANE Select | c.1205_1207delGAA | p.Arg402del | disruptive_inframe_deletion | Exon 8 of 12 | NP_060767.2 | ||
| NGLY1 | NM_001145293.2 | c.1151_1153delGAA | p.Arg384del | disruptive_inframe_deletion | Exon 8 of 12 | NP_001138765.1 | |||
| NGLY1 | NM_001145294.2 | c.1079_1081delGAA | p.Arg360del | disruptive_inframe_deletion | Exon 8 of 12 | NP_001138766.1 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| NGLY1 | ENST00000280700.10 | TSL:1 MANE Select | c.1205_1207delGAA | p.Arg402del | disruptive_inframe_deletion | Exon 8 of 12 | ENSP00000280700.5 | ||
| NGLY1 | ENST00000428257.5 | TSL:1 | c.1151_1153delGAA | p.Arg384del | disruptive_inframe_deletion | Exon 8 of 12 | ENSP00000387430.1 | ||
| NGLY1 | ENST00000308710.9 | TSL:1 | c.1142_1144delGAA | p.Arg381del | disruptive_inframe_deletion | Exon 8 of 12 | ENSP00000307980.5 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
30
GnomAD2 exomes AF: 0.00000796 AC: 2AN: 251162 AF XY: 0.00 show subpopulations
GnomAD2 exomes
AF:
AC:
2
AN:
251162
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461526Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 727054 show subpopulations
GnomAD4 exome
AF:
AC:
2
AN:
1461526
Hom.:
AF XY:
AC XY:
0
AN XY:
727054
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33460
American (AMR)
AF:
AC:
0
AN:
44700
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26118
East Asian (EAS)
AF:
AC:
2
AN:
39670
South Asian (SAS)
AF:
AC:
0
AN:
86228
European-Finnish (FIN)
AF:
AC:
0
AN:
53372
Middle Eastern (MID)
AF:
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1111828
Other (OTH)
AF:
AC:
0
AN:
60382
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
GnomAD4 genome
Cov.:
30
Alfa
AF:
Hom.:
ClinVar
ClinVar submissions as Germline
Significance:Pathogenic
Revision:no assertion criteria provided
Pathogenic
VUS
Benign
Condition
1
-
-
Congenital disorder of deglycosylation (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.