rs139636452
Positions:
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM2BP4_StrongBP6_Very_StrongBS1
The NM_018297.4(NGLY1):c.550G>T(p.Val184Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000347 in 1,612,702 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 (★★).
Frequency
Genomes: 𝑓 0.0017 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00021 ( 0 hom. )
Consequence
NGLY1
NM_018297.4 missense
NM_018297.4 missense
Scores
3
15
Clinical Significance
Conservation
PhyloP100: -0.661
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.007426828).
BP6
Variant 3-25751206-C-A is Benign according to our data. Variant chr3-25751206-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 474226.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00169 (257/152158) while in subpopulation AFR AF= 0.00549 (228/41518). AF 95% confidence interval is 0.00491. There are 0 homozygotes in gnomad4. There are 120 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NGLY1 | NM_018297.4 | c.550G>T | p.Val184Phe | missense_variant | 4/12 | ENST00000280700.10 | NP_060767.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NGLY1 | ENST00000280700.10 | c.550G>T | p.Val184Phe | missense_variant | 4/12 | 1 | NM_018297.4 | ENSP00000280700.5 |
Frequencies
GnomAD3 genomes AF: 0.00170 AC: 258AN: 152042Hom.: 0 Cov.: 33
GnomAD3 genomes
AF:
AC:
258
AN:
152042
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000509 AC: 127AN: 249566Hom.: 0 AF XY: 0.000341 AC XY: 46AN XY: 134950
GnomAD3 exomes
AF:
AC:
127
AN:
249566
Hom.:
AF XY:
AC XY:
46
AN XY:
134950
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000207 AC: 303AN: 1460544Hom.: 0 Cov.: 30 AF XY: 0.000182 AC XY: 132AN XY: 726558
GnomAD4 exome
AF:
AC:
303
AN:
1460544
Hom.:
Cov.:
30
AF XY:
AC XY:
132
AN XY:
726558
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.00169 AC: 257AN: 152158Hom.: 0 Cov.: 33 AF XY: 0.00161 AC XY: 120AN XY: 74382
GnomAD4 genome
AF:
AC:
257
AN:
152158
Hom.:
Cov.:
33
AF XY:
AC XY:
120
AN XY:
74382
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ESP6500AA
AF:
AC:
29
ESP6500EA
AF:
AC:
1
ExAC
AF:
AC:
72
Asia WGS
AF:
AC:
1
AN:
3478
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 14, 2022 | See Variant Classification Assertion Criteria. - |
Congenital disorder of deglycosylation Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 29, 2024 | - - |
NGLY1-related disorder Benign:1
Benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 08, 2024 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
.;T;.;T;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Uncertain
D;D;D;D;D;D
MetaRNN
Benign
T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;M;.;.;.
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N;N;N;D
REVEL
Benign
Sift
Benign
D;D;T;D;D;D
Sift4G
Benign
T;T;T;T;T;.
Polyphen
B;B;B;.;.;.
Vest4
MVP
MPC
0.045
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
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