17-44006266-C-T
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_153006.3(NAGS):c.915+29C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0106 in 1,608,426 control chromosomes in the GnomAD database, including 148 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0097 ( 14 hom., cov: 32)
Exomes 𝑓: 0.011 ( 134 hom. )
Consequence
NAGS
NM_153006.3 intron
NM_153006.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.257
Genes affected
NAGS (HGNC:17996): (N-acetylglutamate synthase) The N-acetylglutamate synthase gene encodes a mitochondrial enzyme that catalyzes the formation of N-acetylglutamate (NAG) from glutamate and acetyl coenzyme-A. NAG is a cofactor of carbamyl phosphate synthetase I (CPSI), the first enzyme of the urea cycle in mammals. This gene may regulate ureagenesis by altering NAG availability and, thereby, CPSI activity. Deficiencies in N-acetylglutamate synthase have been associated with hyperammonemia. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.76).
BP6
Variant 17-44006266-C-T is Benign according to our data. Variant chr17-44006266-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 262689.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-44006266-C-T is described in Lovd as [Likely_benign].
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0097 (1477/152336) while in subpopulation NFE AF= 0.0114 (778/68028). AF 95% confidence interval is 0.0108. There are 14 homozygotes in gnomad4. There are 790 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 14 AR gene
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NAGS | ENST00000293404.8 | c.915+29C>T | intron_variant | 1 | NM_153006.3 | ENSP00000293404.2 | ||||
NAGS | ENST00000589767.1 | c.822+29C>T | intron_variant | 2 | ENSP00000465408.1 | |||||
NAGS | ENST00000592915.1 | n.190+29C>T | intron_variant | 2 |
Frequencies
GnomAD3 genomes AF: 0.00970 AC: 1477AN: 152218Hom.: 14 Cov.: 32
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GnomAD3 exomes AF: 0.00904 AC: 2104AN: 232808Hom.: 29 AF XY: 0.00900 AC XY: 1152AN XY: 128004
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GnomAD4 exome AF: 0.0106 AC: 15500AN: 1456090Hom.: 134 Cov.: 32 AF XY: 0.0103 AC XY: 7488AN XY: 724196
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GnomAD4 genome AF: 0.00970 AC: 1477AN: 152336Hom.: 14 Cov.: 32 AF XY: 0.0106 AC XY: 790AN XY: 74494
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 10, 2018 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
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DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at