rs554503189
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_018297.4(NGLY1):āc.1740A>Gā(p.Thr580=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0001 in 1,613,934 control chromosomes in the GnomAD database, including 3 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 0.000039 ( 0 hom., cov: 32)
Exomes š: 0.00011 ( 3 hom. )
Consequence
NGLY1
NM_018297.4 synonymous
NM_018297.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.167
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
?
Variant 3-25720063-T-C is Benign according to our data. Variant chr3-25720063-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 474216.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.167 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.000107 (156/1461638) while in subpopulation SAS AF= 0.00112 (97/86240). AF 95% confidence interval is 0.000943. There are 3 homozygotes in gnomad4_exome. There are 102 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAdExome4 at 3 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NGLY1 | NM_018297.4 | c.1740A>G | p.Thr580= | synonymous_variant | 11/12 | ENST00000280700.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NGLY1 | ENST00000280700.10 | c.1740A>G | p.Thr580= | synonymous_variant | 11/12 | 1 | NM_018297.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152178Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000167 AC: 42AN: 251200Hom.: 1 AF XY: 0.000206 AC XY: 28AN XY: 135772
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GnomAD4 exome AF: 0.000107 AC: 156AN: 1461638Hom.: 3 Cov.: 31 AF XY: 0.000140 AC XY: 102AN XY: 727128
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GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152296Hom.: 0 Cov.: 32 AF XY: 0.0000806 AC XY: 6AN XY: 74480
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Congenital disorder of deglycosylation Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 18, 2024 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2024 | NGLY1: BP4, BP7 - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at