3-25729184-G-T
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7
The NM_018297.4(NGLY1):c.1560C>A(p.Gly520Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,114 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 Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. G520G) has been classified as Likely benign.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
NGLY1
NM_018297.4 synonymous
NM_018297.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.41
Publications
1 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: Likely_benign. The variant received -3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.44).
BP6
Variant 3-25729184-G-T is Benign according to our data. Variant chr3-25729184-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2850258.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=1.41 with no splicing effect.
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.1560C>A | p.Gly520Gly | synonymous | Exon 10 of 12 | NP_060767.2 | ||
| NGLY1 | NM_001145293.2 | c.1506C>A | p.Gly502Gly | synonymous | Exon 10 of 12 | NP_001138765.1 | |||
| NGLY1 | NM_001145294.2 | c.1434C>A | p.Gly478Gly | synonymous | Exon 10 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.1560C>A | p.Gly520Gly | synonymous | Exon 10 of 12 | ENSP00000280700.5 | ||
| NGLY1 | ENST00000428257.5 | TSL:1 | c.1506C>A | p.Gly502Gly | synonymous | Exon 10 of 12 | ENSP00000387430.1 | ||
| NGLY1 | ENST00000308710.9 | TSL:1 | c.1497C>A | p.Gly499Gly | synonymous | Exon 10 of 12 | ENSP00000307980.5 |
Frequencies
GnomAD3 genomes 0.00000658 AC: 1AN: 151996Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
151996
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
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Gnomad AMR
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Gnomad ASJ
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Gnomad EAS
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Gnomad SAS
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Gnomad FIN
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Gnomad MID
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Gnomad NFE
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Gnomad OTH
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GnomAD2 exomes AF: 0.00000438 AC: 1AN: 228448 AF XY: 0.00000805 show subpopulations
GnomAD2 exomes
AF:
AC:
1
AN:
228448
AF XY:
Gnomad AFR exome
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Gnomad AMR exome
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Gnomad ASJ exome
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Gnomad EAS exome
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Gnomad FIN exome
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Gnomad NFE exome
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Gnomad OTH exome
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GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1396848Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 693802
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1396848
Hom.:
Cov.:
30
AF XY:
AC XY:
0
AN XY:
693802
African (AFR)
AF:
AC:
0
AN:
31066
American (AMR)
AF:
AC:
0
AN:
40068
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
24308
East Asian (EAS)
AF:
AC:
0
AN:
37018
South Asian (SAS)
AF:
AC:
0
AN:
75384
European-Finnish (FIN)
AF:
AC:
0
AN:
50976
Middle Eastern (MID)
AF:
AC:
0
AN:
5540
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1075452
Other (OTH)
AF:
AC:
0
AN:
57036
GnomAD4 genome 0.00000657 AC: 1AN: 152114Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74352 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
152114
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
74352
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41506
American (AMR)
AF:
AC:
0
AN:
15266
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3470
East Asian (EAS)
AF:
AC:
1
AN:
5176
South Asian (SAS)
AF:
AC:
0
AN:
4816
European-Finnish (FIN)
AF:
AC:
0
AN:
10588
Middle Eastern (MID)
AF:
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
AC:
0
AN:
67976
Other (OTH)
AF:
AC:
0
AN:
2110
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
ClinVar
ClinVar submissions as Germline
Significance:Likely benign
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
-
-
1
Congenital disorder of deglycosylation (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
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
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