Menu
GeneBe

3-25783268-G-A

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_018297.4(NGLY1):c.123C>T(p.Asn41=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000381 in 1,608,718 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.00053 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00037 ( 5 hom. )

Consequence

NGLY1
NM_018297.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.26
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]
OXSM (HGNC:26063): (3-oxoacyl-ACP synthase, mitochondrial) This gene encodes a beta-ketoacyl synthetase. The encoded enzyme is required for elongation of fatty acid chains in the mitochondria. Alternatively spliced transcript variants have been described.[provided by RefSeq, Feb 2009]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.41).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 3-25783268-G-A is Benign according to our data. Variant chr3-25783268-G-A is described in ClinVar as [Benign]. Clinvar id is 474208.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=2.26 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000532 (81/152286) while in subpopulation EAS AF= 0.0147 (76/5168). AF 95% confidence interval is 0.012. There are 0 homozygotes in gnomad4. There are 43 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAdExome at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NGLY1NM_018297.4 linkuse as main transcriptc.123C>T p.Asn41= synonymous_variant 1/12 ENST00000280700.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NGLY1ENST00000280700.10 linkuse as main transcriptc.123C>T p.Asn41= synonymous_variant 1/121 NM_018297.4 P1Q96IV0-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000532
AC:
81
AN:
152168
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.000288
Gnomad EAS
AF:
0.0147
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00103
AC:
250
AN:
243856
Hom.:
2
AF XY:
0.000866
AC XY:
115
AN XY:
132868
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.000305
Gnomad EAS exome
AF:
0.0132
Gnomad SAS exome
AF:
0.000197
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000547
Gnomad OTH exome
AF:
0.000337
GnomAD4 exome
AF:
0.000365
AC:
532
AN:
1456432
Hom.:
5
Cov.:
34
AF XY:
0.000362
AC XY:
262
AN XY:
724666
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000449
Gnomad4 ASJ exome
AF:
0.000154
Gnomad4 EAS exome
AF:
0.0119
Gnomad4 SAS exome
AF:
0.000267
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000144
Gnomad4 OTH exome
AF:
0.000399
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000532
AC:
81
AN:
152286
Hom.:
0
Cov.:
32
AF XY:
0.000578
AC XY:
43
AN XY:
74458
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.000288
Gnomad4 EAS
AF:
0.0147
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000134
Hom.:
0
Bravo
AF:
0.00114
Asia WGS
AF:
0.00260
AC:
9
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Congenital disorder of deglycosylation Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJan 29, 2024- -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxJul 08, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.41
Cadd
Benign
14
Dann
Benign
0.96
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.070
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: rs142425326; hg19: chr3-25824759; API