rs104894604
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PVS1PP5
The NM_153006.3(NAGS):c.971G>A(p.Trp324Ter) variant causes a stop gained change involving the alteration of a conserved nucleotide. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
NAGS
NM_153006.3 stop_gained
NM_153006.3 stop_gained
Scores
4
2
1
Clinical Significance
Conservation
PhyloP100: 7.86
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 Likely_pathogenic. Variant got 9 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PP5
?
Variant 17-44006584-G-A is Pathogenic according to our data. Variant chr17-44006584-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 2428.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr17-44006584-G-A is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NAGS | NM_153006.3 | c.971G>A | p.Trp324Ter | stop_gained | 4/7 | ENST00000293404.8 | |
NAGS | XM_011524438.2 | c.971G>A | p.Trp324Ter | stop_gained | 4/6 | ||
NAGS | XM_011524439.2 | c.473G>A | p.Trp158Ter | stop_gained | 4/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NAGS | ENST00000293404.8 | c.971G>A | p.Trp324Ter | stop_gained | 4/7 | 1 | NM_153006.3 | P1 | |
NAGS | ENST00000589767.1 | c.878G>A | p.Trp293Ter | stop_gained | 4/7 | 2 | |||
NAGS | ENST00000592915.1 | n.246G>A | non_coding_transcript_exon_variant | 2/4 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1439140Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0AN XY: 714046
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1439140
Hom.:
Cov.:
36
AF XY:
AC XY:
0
AN XY:
714046
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Hyperammonemia, type III Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jun 01, 2003 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
A
Vest4
GERP RS
Splicing
Name
Calibrated prediction
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DG_spliceai
Position offset: 1
Find out detailed SpliceAI scores and Pangolin per-transcript scores at