17-44006266-C-T

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

Scores

2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.257
Variant links:
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

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NAGSNM_153006.3 linkc.915+29C>T intron_variant ENST00000293404.8 NP_694551.1 Q8N159
NAGSXM_011524438.2 linkc.915+29C>T intron_variant XP_011522740.1
NAGSXM_011524439.2 linkc.417+29C>T intron_variant XP_011522741.1 Q2NKP2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NAGSENST00000293404.8 linkc.915+29C>T intron_variant 1 NM_153006.3 ENSP00000293404.2 Q8N159
NAGSENST00000589767.1 linkc.822+29C>T intron_variant 2 ENSP00000465408.1 K7EK11
NAGSENST00000592915.1 linkn.190+29C>T intron_variant 2

Frequencies

GnomAD3 genomes
AF:
0.00970
AC:
1477
AN:
152218
Hom.:
14
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00222
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0101
Gnomad ASJ
AF:
0.00720
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0389
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0114
Gnomad OTH
AF:
0.00670
GnomAD3 exomes
AF:
0.00904
AC:
2104
AN:
232808
Hom.:
29
AF XY:
0.00900
AC XY:
1152
AN XY:
128004
show subpopulations
Gnomad AFR exome
AF:
0.00172
Gnomad AMR exome
AF:
0.00367
Gnomad ASJ exome
AF:
0.00508
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0367
Gnomad NFE exome
AF:
0.0110
Gnomad OTH exome
AF:
0.00642
GnomAD4 exome
AF:
0.0106
AC:
15500
AN:
1456090
Hom.:
134
Cov.:
32
AF XY:
0.0103
AC XY:
7488
AN XY:
724196
show subpopulations
Gnomad4 AFR exome
AF:
0.00138
Gnomad4 AMR exome
AF:
0.00355
Gnomad4 ASJ exome
AF:
0.00716
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000234
Gnomad4 FIN exome
AF:
0.0331
Gnomad4 NFE exome
AF:
0.0116
Gnomad4 OTH exome
AF:
0.00849
GnomAD4 genome
AF:
0.00970
AC:
1477
AN:
152336
Hom.:
14
Cov.:
32
AF XY:
0.0106
AC XY:
790
AN XY:
74494
show subpopulations
Gnomad4 AFR
AF:
0.00221
Gnomad4 AMR
AF:
0.0101
Gnomad4 ASJ
AF:
0.00720
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0389
Gnomad4 NFE
AF:
0.0114
Gnomad4 OTH
AF:
0.00663
Alfa
AF:
0.00827
Hom.:
0
Bravo
AF:
0.00695
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

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 submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingGeneDxJul 10, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.76
CADD
Benign
1.1
DANN
Benign
0.84

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: rs146451392; hg19: chr17-42083634; API