dbSNP rs228771: NAGS:c.1096+20C>G (chr17-44006729-C-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_153006.3(NAGS):c.1096+20C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.388 in 1,579,606 control chromosomes in the GnomAD database, including 130,060 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.29 ( 8719 hom., cov: 31)

Exomes 𝑓: 0.40 ( 121341 hom. )

Consequence

NAGS
NM_153006.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -3.49

Publications

14 publications found

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 Gene-Disease associations (from GenCC):

hyperammonemia due to N-acetylglutamate synthase deficiency
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Labcorp Genetics (formerly Invitae), ClinGen

NAGS links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_153006.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 17-44006729-C-G is Benign according to our data. Variant chr17-44006729-C-G is described in ClinVar as Benign. ClinVar VariationId is 262687.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.433 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153006.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAGS	NM_153006.3	MANE Select	c.1096+20C>G		intron	N/A	NP_694551.1	Q8N159

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NAGS	ENST00000293404.8	TSL:1 MANE Select	c.1096+20C>G	intron	N/A	ENSP00000293404.2	Q8N159
NAGS	ENST00000906978.1		c.1111+20C>G	intron	N/A	ENSP00000577037.1
NAGS	ENST00000589767.1	TSL:2	c.1003+20C>G	intron	N/A	ENSP00000465408.1	K7EK11

Frequencies

GnomAD3 genomes

AF:

0.294

AC:

44700

AN:

151908

Hom.:

8717

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0782

Gnomad AMI

AF:

0.437

Gnomad AMR

AF:

0.278

Gnomad ASJ

AF:

0.444

Gnomad EAS

AF:

0.0172

Gnomad SAS

AF:

0.266

Gnomad FIN

AF:

0.311

Gnomad MID

AF:

0.519

Gnomad NFE

AF:

0.437

Gnomad OTH

AF:

0.369

GnomAD2 exomes

AF:

0.309

AC:

68129

AN:

220622

AF XY:

0.324

show subpopulations

Gnomad AFR exome

AF:

0.0683

Gnomad AMR exome

AF:

0.194

Gnomad ASJ exome

AF:

0.451

Gnomad EAS exome

AF:

0.0167

Gnomad FIN exome

AF:

0.310

Gnomad NFE exome

AF:

0.432

Gnomad OTH exome

AF:

0.376

GnomAD4 exome

AF:

0.398

AC:

568093

AN:

1427580

Hom.:

121341

Cov.:

AF XY:

0.396

AC XY:

279521

AN XY:

705122

show subpopulations

African (AFR)

AF:

0.0685

AC:

2264

AN:

33052

American (AMR)

AF:

0.207

AC:

9028

AN:

43578

Ashkenazi Jewish (ASJ)

AF:

0.447

AC:

11144

AN:

24918

East Asian (EAS)

AF:

0.0106

AC:

415

AN:

39176

South Asian (SAS)

AF:

0.274

AC:

22864

AN:

83314

European-Finnish (FIN)

AF:

0.322

AC:

15959

AN:

49638

Middle Eastern (MID)

AF:

0.494

AC:

2202

AN:

4456

European-Non Finnish (NFE)

AF:

0.442

AC:

482415

AN:

1090680

Other (OTH)

AF:

0.371

AC:

21802

AN:

58768

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

15098

30196

45295

60393

75491

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14354

28708

43062

57416

71770

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.294

AC:

44680

AN:

152026

Hom.:

8719

Cov.:

AF XY:

0.286

AC XY:

21242

AN XY:

74298

show subpopulations

African (AFR)

AF:

0.0779

AC:

3232

AN:

41494

American (AMR)

AF:

0.277

AC:

4232

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.444

AC:

1539

AN:

3468

East Asian (EAS)

AF:

0.0170

AC:

AN:

5166

South Asian (SAS)

AF:

0.266

AC:

1281

AN:

4822

European-Finnish (FIN)

AF:

0.311

AC:

3287

AN:

10570

Middle Eastern (MID)

AF:

0.524

AC:

154

AN:

294

European-Non Finnish (NFE)

AF:

0.437

AC:

29706

AN:

67928

Other (OTH)

AF:

0.364

AC:

767

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1410

2820

4229

5639

7049

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

440

880

1320

1760

2200

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.299

Hom.:

1363

Bravo

AF:

0.283

Asia WGS

AF:

0.156

AC:

544

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (4)

Hyperammonemia, type III (3)

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.024

(source)

DANN

Benign

0.61

PhyloP100

-3.5

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over