chr3-25720081-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_018297.4(NGLY1):ā€‹c.1722A>Gā€‹(p.Gln574=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00235 in 1,613,902 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā˜…ā˜…).

Frequency

Genomes: š‘“ 0.0013 ( 0 hom., cov: 32)
Exomes š‘“: 0.0025 ( 7 hom. )

Consequence

NGLY1
NM_018297.4 synonymous

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.458
Variant links:
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 -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.59).
BP6
Variant 3-25720081-T-C is Benign according to our data. Variant chr3-25720081-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 381455.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.458 with no splicing effect.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00133 (202/152274) while in subpopulation NFE AF= 0.00248 (169/68020). AF 95% confidence interval is 0.00218. There are 0 homozygotes in gnomad4. There are 93 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAdExome4 at 7 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NGLY1NM_018297.4 linkuse as main transcriptc.1722A>G p.Gln574= synonymous_variant 11/12 ENST00000280700.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NGLY1ENST00000280700.10 linkuse as main transcriptc.1722A>G p.Gln574= synonymous_variant 11/121 NM_018297.4 P1Q96IV0-1

Frequencies

GnomAD3 genomes
AF:
0.00133
AC:
202
AN:
152156
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000410
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000589
Gnomad ASJ
AF:
0.000576
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000377
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00248
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.00149
AC:
375
AN:
251226
Hom.:
1
AF XY:
0.00154
AC XY:
209
AN XY:
135778
show subpopulations
Gnomad AFR exome
AF:
0.000123
Gnomad AMR exome
AF:
0.000925
Gnomad ASJ exome
AF:
0.00119
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000980
Gnomad FIN exome
AF:
0.000277
Gnomad NFE exome
AF:
0.00273
Gnomad OTH exome
AF:
0.00163
GnomAD4 exome
AF:
0.00245
AC:
3588
AN:
1461628
Hom.:
7
Cov.:
31
AF XY:
0.00239
AC XY:
1740
AN XY:
727122
show subpopulations
Gnomad4 AFR exome
AF:
0.000478
Gnomad4 AMR exome
AF:
0.000939
Gnomad4 ASJ exome
AF:
0.00111
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000128
Gnomad4 FIN exome
AF:
0.000431
Gnomad4 NFE exome
AF:
0.00302
Gnomad4 OTH exome
AF:
0.00174
GnomAD4 genome
AF:
0.00133
AC:
202
AN:
152274
Hom.:
0
Cov.:
32
AF XY:
0.00125
AC XY:
93
AN XY:
74454
show subpopulations
Gnomad4 AFR
AF:
0.000409
Gnomad4 AMR
AF:
0.000588
Gnomad4 ASJ
AF:
0.000576
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000377
Gnomad4 NFE
AF:
0.00248
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.00211
Hom.:
0
Bravo
AF:
0.00138
EpiCase
AF:
0.00295
EpiControl
AF:
0.00332

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:3
Likely benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenJun 01, 2023NGLY1: BP4, BP7 -
Likely benign, criteria provided, single submitterclinical testingGeneDxDec 15, 2020- -
Congenital disorder of deglycosylation Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpFeb 01, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.59
CADD
Benign
2.1
DANN
Benign
0.39

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs74650888; hg19: chr3-25761572; API