Variant 17-44006266-C-T details in Genebe, Genetics Data Aggregator

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

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]

NAGS links:

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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	Effect	MANE	Protein	UniProt
NAGS	NM_153006.3 link	c.915+29C>T	intron_variant	ENST00000293404.8	NP_694551.1	Q8N159
NAGS	XM_011524438.2 link	c.915+29C>T	intron_variant		XP_011522740.1
NAGS	XM_011524439.2 link	c.417+29C>T	intron_variant		XP_011522741.1	Q2NKP2

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
NAGS	ENST00000293404.8 link	c.915+29C>T	intron_variant	1	NM_153006.3	ENSP00000293404.2	Q8N159
NAGS	ENST00000589767.1 link	c.822+29C>T	intron_variant	2		ENSP00000465408.1	K7EK11
NAGS	ENST00000592915.1 link	n.190+29C>T	intron_variant	2

Frequencies

GnomAD3 genomes

AF:

0.00970

AC:

1477

AN:

152218

Hom.:

Cov.:

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.:

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.:

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.:

Cov.:

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.:

Bravo

AF:

0.00695

Asia WGS

AF:

0.000289

AC:

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 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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over